Deficient brain GABA metabolism leads to widespread impairments of astrocyte and oligodendrocyte function
Open accessAbstract
The neurometabolic disorder succinic semialdehyde dehydrogenase (SSADH) deficiency leads to great neurochemical imbalances and severe neurological manifestations. The cause of the disease is loss of function of the enzyme SSADH, leading to impaired metabolism of the principal inhibitory neurotransmitter GABA. Despite the known identity of the enzymatic deficit, the underlying pathology of SSADH deficiency remains unclear. To uncover new mechanisms of the disease, we performed an untargeted integrative analysis of cerebral protein expression, functional metabolism, and lipid composition in a genetic mouse model of SSADH deficiency (ALDH5A1 knockout mice). Our proteomic analysis revealed a clear regional vulnerability, as protein alterations primarily manifested in the hippocampus and cerebral cortex of the ALDH5A1 knockout mice. These regions displayed aberrant expression of proteins linked to amino acid homeostasis, mitochondria, glial function, and myelination. Stable isotope tracing in acutely isolated brain slices demonstrated an overall maintained oxidative metabolism of glucose, but a selective decrease in astrocyte metabolic activity in the cerebral cortex of ALDH5A1 knockout mice. In contrast, an elevated capacity of oxidative glutamine metabolism was observed in the ALDH5A1 knockout brain, which may serve as a neuronal compensation of impaired astrocyte glutamine provision. In addition to reduced expression of critical oligodendrocyte proteins, a severe depletion of myelin‐enriched sphingolipids was found in the brains of ALDH5A1 knockout mice, suggesting degeneration of myelin. Altogether, our study highlights that impaired astrocyte and oligodendrocyte function is intimately linked to SSADH deficiency pathology, suggesting that selective targeting of glial cells may hold therapeutic potential in this disease.
AI snapshot
Written from the paper’s full text.
TL;DR
Deficient GABA metabolism in ALDH5A1 knockout mice causes regional brain proteomic, metabolic, and lipidomic changes centered on astrocytes and oligodendrocytes. The study links SSADH deficiency pathology to impaired astrocyte energetics, altered glutamate/glutamine metabolism, and myelin lipid depletion.
Key findings
- Regional proteomic vulnerability: 7,615 protein groups identified; 169 proteins increased and 200 decreased across brain regions, with cortex, hippocampus, and cerebellum showing 157, 296, and 20 changes, respectively. Seven proteins were upregulated and five downregulated in all three regions.
- Amino acid imbalance: GABA increased 6.3-fold in cerebral cortex and 5.7-fold in hippocampus; glutamine decreased 2.0-fold in cortex and 1.5-fold in hippocampus; aspartate, serine, alanine, and taurine were also elevated.
- Metabolic impairments: oxidative glucose metabolism was maintained, but [1,2-13C]acetate metabolism was reduced in ALDH5A1 KO cerebral cortical slices, indicating impaired astrocyte energetics; [U-13C]glutamine direct metabolism was elevated in cortex and hippocampus, while hippocampal [U-13C]glutamate metabolism was reduced.
- Lipid/myelin disruption: 525 unique lipid species quantified; cortex had 166 altered lipids (36 increased, 130 decreased) and hippocampus had 143 altered lipids (16 increased, 127 decreased). Myelin-enriched Hex1Cer and sulfatides were reduced, alongside lower MBP, MAG, MOG, and PLP1 protein expression.
Methods
- ALDH5A1 knockout and wild-type littermate mice were used at 16–18 days of age; total n = 53 mice (26 KO: 12 male, 14 female; 27 wild-type: 17 male, 10 female). Proteomics used 8 KO and 10 wild-type mice; amino acid analysis 10 KO and 10 wild-type; brain slice isotope tracing 8 KO and 7 wild-type; lipidomics 10 KO and 10 wild-type.
- Untargeted regional proteomics was performed on cerebral cortex, hippocampus, and cerebellum using diaPASEF timsTOF mass spectrometry with Spectronaut and Clinical Knowledge Graph analysis. Amino acids were quantified by HPLC, stable isotope tracing used acutely isolated brain slices with [U-13C]GABA, [U-13C]glucose, [1,2-13C]acetate, [U-13C]glutamate, or [U-13C]glutamine followed by GC-MS, and untargeted lipidomics used LC-MS.
- Statistical comparisons used two-tailed unpaired Student’s t-tests with Benjamini-Hochberg correction at FDR < 0.05; data are presented as mean ± SEM, with PCA, hierarchical clustering, and enrichment analyses for proteomic data.
Limitations
- The paper states that microglia were not addressed and must be investigated in SSADH deficiency; it also notes that the cerebellum showed few proteomic changes but may still be involved in the disease.
- The paper states that no randomization was applied because two defined littermate groups were used continuously, and KO mice were studied at 16–18 days of age to avoid generalized seizures.
- Evident from the text: findings are from a genetic mouse model only, with no human tissue or causal validation; several analyses rely on modest sample sizes (n = 7–10 per group), and sex-specific effects are not reported despite inclusion of both sexes.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
8 of 25 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Elevated GFAP expression has been observed in ALDH5A1 KO mice and patient brain tissue.
“Elevated GFAP expression, a marker of astrogliosis, has been observed in both ALDH5A1 KO mice (Brown, Gibson, et al., 2020;Hogema et al., 2001) and patient brain tissue (Walters et al., 2021).”
Quote in the paperNot a substantial claim1 of 3 sources checked- cites Brown, Gibson, et al., 2020
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites Hogema et al., 2001 source
- cites Walters et al., 2021 source
The Results report reactive astrogliosis in the patient’s cortex and hippocampus, assessed by GFAP immunohistochemistry. This supports the patient-brain finding, but the paper does not report a measured increase in GFAP expression. The mouse finding has separate citations and is not the part attributed to Walters et al. (LLM, conf=0.83)
Experimental — accuracy not yet measured
- Premisecitation
Astrocytes become reactive in SSADH deficiency.
“Astrocytes become reactive in SSADH deficiency (Brown, Gibson, et al., 2020;Hogema et al., 2001;Walters et al., 2021)”
Quote in the paperSubstantial claim1 of 3 sources checked - Premisecitation
Loss of SSADH function leads to an increased number of morphologically abnormal mitochondria in the brain.
“Loss of SSADH function leads to an increased number of morphologically abnormal mitochondria in the brain (Lakhani et al., 2014)”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Lakhani et al., 2014 source
The Results report increased mitochondrial numbers in the brains of SSADH-deficient mice, but the morphological differences measured by electron microscopy were in liver mitochondria. The Discussion likewise identifies larger mitochondria specifically in the liver; our copy does not establish that the brain mitochondria were morphologically abnormal. (LLM, conf=0.90)
Experimental — accuracy not yet measured
- Premisecitation
Elevated aspartate levels have been confirmed in cerebrospinal fluid and brain tissue of SSADH deficient patients.
“elevated aspartate levels have been confirmed in both cerebrospinal fluid and brain tissue of SSADH deficient patients (Kirby, Walters, Brown, et al., 2020;Peters et al., 2023)”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites Kirby, Walters, Brown, et al., 2020 source
The Results (Amino acid analyses using the MassTrak system; page not provided) report significantly elevated aspartic acid in the patient's brain tissue. The paper does not report elevated aspartate in cerebrospinal fluid, so it supports only the brain-tissue part of the claim. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites Peters et al., 2023 source
- Interpretationcitation
Increased levels of sphingosines indicate elevated myelin metabolism in ALDH5A1 KO mice.
“However, the increased levels of sphingosines also indicate elevated myelin metabolism, as sphingosines provide the backbone of Hex1Cer and sulfatides, and thus accumulate when sphingolipids are broken down (Marian et al., 2023).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Marian et al., 2023 source
The Discussion (page unavailable) calls sphingosine a sphingolipid catabolic intermediate and says its increase could reflect accelerated myelin breakdown. It also says accumulation could instead result from blocked lysosomal catabolism; the paper does not establish elevated myelin metabolism in ALDH5A1 knockout mice. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Interpretationcitation
Early and sustained disruptions of GABA signaling are likely a key factor of perturbed oligodendrocyte development and faulty myelination in SSADH deficiency.
“As GABA already accumulate during embryonic development in SSADH deficiency (Jansen et al., 2008), early and sustained disruptions of GABA signaling is likely a key factor of perturbed oligodendrocyte development and faulty myelination in SSADH deficiency.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Jansen et al., 2008 source
- Findingown data
A clear reduction of [1,2-13C]acetate metabolism was found in the cerebral cortex of ALDH5A1 KO mice.
“Here we found a clear reduction of [1,2-13 C]acetate metabolism in the cerebral cortex of ALDH5A1 KO mice”
Quote in the paperSubstantial claim- Rests on an assumption: [1,2-13C]Acetate is primarily metabolized in astrocytes.
- Findingown data
Oxidative metabolism of [U-13C]glucose is preserved in the ALDH5A1 KO brain.
“Oxidative metabolism of [U-13 C]glucose was preserved in the ALDH5A1 KO brain.”
- Also stated in: § 3.5 | Lipidomic analysis reveals extensive changes in brain lipid composition · plain
“Preserved oxidative glucose metabolism in ALDH5A1 knockout brain.”
Quote in the paperSubstantial claim - Also stated in: § 3.5 | Lipidomic analysis reveals extensive changes in brain lipid composition · plain
- Findingown data
Over 80% of all Hex1Cer species display significantly reduced abundance in the ALDH5A1 KO brain.
“over 80% of all Hex1Cer species displayed significantly reduced abundance in the ALDH5A1 KO brain.”
Quote in the paperSubstantial claim - Findingown data
The hippocampus of ALDH5A1 KO mice additionally displayed a reduction in total sulfatides (ST) and dihexosylceramide.
“All of these lipid classes were dysregulated similarly in the hippocampus of ALDH5A1 KO mice, which additionally displayed a reduction in total sulfatides (ST), dihexosylceramide”
Quote in the paperNot a substantial claim - Findingown data
Expression of proteins related to oligodendrocyte function and myelination is severely reduced in the ALDH5A1 KO brain, including MBP and PLP1.
“Expression of proteins related to oligodendrocyte function and myelination was severely reduced in the ALDH5A1 KO brain, including MBP and PLP1”
- Also stated in: § 5 | CONCLUSIONS · plain
“proteins for oligodendrocyte function and myelination displayed lower expression in the ALDH5A1 KO mice, including the myelin proteins myelin basic protein (MBP), myelin-associated glycoprotein (MAG), myelin-oligodendrocyte glycoprotein (MOG), and myelin proteolipid protein (PLP1), and the oligodendrocyte-specific markers aspartoacylase (ASPA), 2-hydroxyacylsphingosine 1-beta-galactosyltransferase”
Quote in the paperSubstantial claim - Also stated in: § 5 | CONCLUSIONS · plain
- Findingown data
In ALDH5A1 KO mice, the cerebral cortex and hippocampus are most affected at the proteomic level.
“Overall, we found that the cerebral cortex and hippocampus were most affected at the proteomic level in the ALDH5A1 KO mice.”
Quote in the paperNot a substantial claim - Findingown data
GFAP expression was elevated in the ALDH5A1 knockout brain.
“showing elevated expression of glial fibrillary acid protein (GFAP)”
Quote in the paperSubstantial claim - Findingown data
All of these lipid classes were dysregulated similarly in the hippocampus of ALDH5A1 KO mice.
“All of these lipid classes were dysregulated similarly in the hippocampus of ALDH5A1 KO mice, which additionally displayed a reduction in total sulfatides (ST), dihexosylceramide”
Quote in the paperNot a substantial claim - Findingown data
ALDH5A1 KO mice show increased expression of SLC3A2 and SLC7A5.
“increased expression of SLC3A2 and SLC7A5, facilitating uptake of neutral amino acids.”
- Also stated in: § 5 | CONCLUSIONS · plain
“Two components of a heterodimer transport complex, SLC3A2 and SLC7A5, mediating high-affinity uptake of multiple amino acids, were upregulated in both regions of the ALDH5A1 KO mice.”
Quote in the paperSubstantial claim - Also stated in: § 5 | CONCLUSIONS · plain
- Findingown data
ALDH5A1 KO mice show reduced expression of SLC7A1 and SLC7A3 in the cerebral cortex.
“reduced expression of SLC7A1 and SLC7A3, mediating transport of arginine, lysine, and ornithine was found in the cerebral cortex”
Quote in the paperNot a substantial claim - Findingown data
Several amino acid transporters were perturbed in ALDH5A1 KO mice.
“several amino acid transporters were perturbed in the ALDH5A1 KO mice”
Quote in the paperNot a substantial claim - Findingown data
Glutamate M+5 was unaltered in ALDH5A1 KO slices.
“Glutamate M + 5 was unaltered in the ALDH5A1 KO slices (Figure 4), suggesting a maintained uptake capacity of exogenous glutamate.”
Quote in the paperNot a substantial claim - Findingown data
Lipidomic analysis including sphingolipids revealed alterations of multiple total lipid classes and a much larger number of reduced lipids than increased lipid species in ALDH5A1 KO mice.
“our lipidomic analysis including sphingolipids, revealed alterations of multiple total lipid classes and a much larger number of reduced lipids in comparison with increased lipid species.”
Quote in the paperSubstantial claim - Findingown data
The most dysregulated lipids in the ALDH5A1 knockout mouse brain primarily belonged to the Hex1Cer, Cer, ST, LPE, and LPC classes.
“The most dysregulated lipids in the ALDH5A1 KO mice primarily belonged to the Hex1Cer, Cer, ST, LPE, and lysophosphatidylcholine (LPC) classes.”
Quote in the paperSubstantial claim - Findingown data
Levels of aspartate, serine, alanine, and taurine were elevated in both cerebral cortex and hippocampus of ALDH5A1 KO mice.
“The levels of several other amino acids were also elevated in both regions of the ALDH5A1 KO mice, including aspartate, serine, alanine, and taurine (Table 1).”
Quote in the paperNot a substantial claim - Findingown data
The hippocampus of ALDH5A1 KO mice was clearly the most affected region.
“The hippocampus of the ALDH5A1 KO mice was clearly the most affected region”
Quote in the paperSubstantial claim - Findingown data
Pathway enrichment analyses identified upregulation of L-serine and L-proline biosynthetic processes and mitochondrial proteins in both cerebral cortex and hippocampus.
“Several common terms were identified in both regions, including upregulation of L-serine and L-proline biosynthetic processes and mitochondrial proteins.”
Quote in the paperSubstantial claim - Findingown data
A decreased capacity for [U-13C]glutamate metabolism was found in the ALDH5A1 KO hippocampus.
“A decreased capacity for [U-13 C]glutamate metabolism was found in the ALDH5A1 KO hippocampus.”
- Also stated in: § 4.1 | Proteomic changes and amino acid homeostasis · plain
“Hippocampal glutamate metabolism is reduced in ALDH5A1 knockout mice.”
Quote in the paperSubstantial claim - Also stated in: § 4.1 | Proteomic changes and amino acid homeostasis · plain
- Findingown data
Critical proteins of the GABAergic synapse were strongly dysregulated in ALDH5A1 KO mice, including reduced GAT3, GAD1, GAD2, and GABBR2 in both cerebral cortex and hippocampus.
“critical proteins of the GABAergic synapse were also strongly dysregulated including reduced expression of the GABA transporter GAT3 (SLC6A11), both isoforms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD1 & GAD2) and a GABA B receptor subunit (GABBR2) in both the cerebral cortex and hippocampus of ALDH5A1 KO mice.”
Quote in the paperSubstantial claim - Findingown data
Total sphingosines (Sph) and diacylglycerols (DAG) were increased in the cerebral cortex of ALDH5A1 KO mice.
“Total levels of monohexosylceramides (Hex1Cer), lysophosphatidylethanolamines (LPE), and acylcarnitines (AcCa) were significantly reduced, whereas total sphingosines (Sph) and diacylglyerols (DAG) were increased in the cerebral cortex of ALDH5A1 KO mice (Figure 6a).”
Quote in the paperNot a substantial claim - Findingown data
Essential (SLC1A2) and GLAST (SLC1A3) was lower in the ALDH5A1 KO hippocampus.
“In particular, essential (SLC1A2) and GLAST (SLC1A3) was lower in the ALDH5A1 KO hippocampus.”
Quote in the paperSubstantial claim - Findingown data
No change in glutamine M+5 was observed in ALDH5A1 KO slices.
“No change in glutamine M + 5 was observed (Figure 5), suggesting a maintained glutamine uptake capacity in both regions.”
Quote in the paperSubstantial claim - Findingown data
Regional proteomic analysis of the ALDH5A1 KO brain revealed multiple changes in proteins related to homeostasis of other amino acids.
“The regional proteomic analysis of the ALDH5A1 KO brain further revealed multiple changes in proteins related to homeostasis of other amino acids.”
Quote in the paperNot a substantial claim - Findingown data
The ALDH5A1 KO cerebral cortex displayed 166 altered lipids (36 increased, 130 decreased).
“At the level of individual lipids, the ALDH5A1 KO cerebral cortex displayed 166 altered lipids (36 increased, 130 decreased)”
Quote in the paperSubstantial claim - Findingcitation
Reduced acylcarnitine species in the ALDH5A1 KO brain correlate with lower acylcarnitine levels in plasma and brain samples of SSADH deficiency patients.
“our findings of reduced acylcarnitine species in the ALDH5A1 KO brain correlate well with the consistent lower levels of acylcarnitines found in both plasma and brain samples of SSADH deficiency patients”
Quote in the paperNot a substantial claim - Findingown data
Across the three brain regions, 169 proteins had increased expression and 200 had decreased expression in ALDH5A1 KO compared to wild-type mice.
“Across the three brain regions, we identified 169 and 200 proteins with increased or decreased expression, respectively, when comparing ALDH5A1 KO to wild-type mice.”
Quote in the paperSubstantial claim - Findingown data
Brain proteome of ALDH5A1 knockout mice reveals extensive regional alterations in protein expression levels.
“Brain proteome of ALDH5A1 knockout mice reveals extensive regional alterations in protein expression levels.”
Quote in the paperSubstantial claim - Findingown data
The ALDH5A1 KO cerebral cortex, hippocampus, and cerebellum displayed 157, 296, and 20 protein changes, respectively.
“Specifically, the ALDH5A1 KO cerebral cortex, hippocampus, and cerebellum displayed 157, 296, and 20 protein changes, respectively (Figure 1a, Data S1).”
Quote in the paperNot a substantial claim - Findingown data
The ALDH5A1 KO brain proteome shows extensive changes related to amino acid homeostasis, mitochondria, and glial function.
“The brain proteome revealed extensive changes related to amino acid homeostasis, mitochondria, and glial function.”
Quote in the paperSubstantial claim - Findingown data
Glutamate uptake capacity appears maintained in the ALDH5A1 KO brain.
“as glutamate M + 5, reflecting functional glutamate uptake, was unaltered, glutamate uptake capacity appears maintained in the ALDH5A1 KO brain.”
Quote in the paperNot a substantial claim- Rests on an assumption: Cellular uptake of [U-13C]glutamate leads to M+5 enrichment of the intracellular glutamate pool, reflecting glutamate uptake.
- Findingown data
Faulty lipid metabolism in the ALDH5A1 KO brain is supported by upregulation of several proteins related to peroxisomes.
“Faulty lipid metabolism in the ALDH5A1 KO brain is supported by upregulation of several proteins related to peroxisomes (Data S1)”
Quote in the paperNot a substantial claim - Findingown data
ALDH5A1 KO mice show increased expression of alanine aminotransferase (GPT2/ALAT) in the hippocampus.
“increased expression of alanine aminotransferase (GPT2/ ALAT) in the hippocampus of ALDH5A1 KO mice”
Quote in the paperNot a substantial claim - Findingown data
Glutamine was the only amino acid displaying reduced abundance in ALDH5A1 KO mice (2.0-fold decrease in cerebral cortex and 1.5-fold decrease in hippocampus).
“In contrast, glutamine was the only amino acid displaying reduced abundance in the ALDH5A1 KO mice (2.0-fold decrease in cerebral cortex and 1.5-fold decrease in hippocampus).”
Quote in the paperNot a substantial claim - Findingown data
ALDH5A1 KO mice show lower expression of the serine transporter SLC7A10 in both hippocampus and cerebral cortex.
“expression of the serine transporter SLC7A10 was lower in both the hippocampus and cerebral cortex of the ALDH5A1 KO mice.”
- Also stated in: § 5 | CONCLUSIONS · plain
“In contrast, expression of a major transporter of serine and glycine, SLC7A10, was decreased.”
Quote in the paperNot a substantial claim - Also stated in: § 5 | CONCLUSIONS · plain
- Findingown data
ALDH5A1 KO mice displayed severe accumulation of GABA in both cerebral cortex (6.3-fold increase) and hippocampus (5.7-fold increase).
“As expected, the ALDH5A1 KO mice displayed a severe accumulation of GABA in both cerebral cortex (6.3-fold increase) and hippocampus (5.7-fold increase).”
Quote in the paperSubstantial claim - Findingown data
The ALDH5A1 KO hippocampus proteome shows changes in astrocyte-specific metabolic proteins, including glycogen synthase (GYS1) and pyruvate carboxylase (PCX).
“The proteome also revealed several changes in astrocyte-specific metabolic proteins in the ALDH5A1 KO hippocampus, including glycogen synthase (GYS1) and pyruvate carboxylase (PCX)”
Quote in the paperSubstantial claim - Findingown data
Terms related to myelin, myelination, and CNS development displayed decreased expression in both cerebral cortex and hippocampus.
“In contrast, terms related to myelin, myelination, and CNS development displayed decreased expression in both regions.”
Quote in the paperSubstantial claim - Findingown data
In ALDH5A1 knockout mice, 143 lipid changes were displayed compared to wild-type control, with 16 increased and 127 decreased.
“displayed 143 lipid changes (16 increased, 127 decreased) when compared to wild-type control (Figure6b).”
Quote in the paperSubstantial claim - Findingown data
ALDH5A1 KO brain shows marked upregulation of mitochondrial proteins.
“Our proteomic analysis revealed a marked upregulation of mitochondrial proteins in the ALDH5A1 KO brain”
Quote in the paperNot a substantial claim - Findingown data
Several myelin-enriched lipids were depleted in the ALDH5A1 knockout brain.
“In addition several myelin-enriched lipids were depleted”
Quote in the paperSubstantial claim - Findingown data
Total levels of monohexosylceramides (Hex1Cer), lysophosphatidylethanolamines (LPE), and acylcarnitines (AcCa) were significantly reduced in the cerebral cortex of ALDH5A1 KO mice.
“Total levels of monohexosylceramides (Hex1Cer), lysophosphatidylethanolamines (LPE), and acylcarnitines (AcCa) were significantly reduced, whereas total sphingosines (Sph) and diacylglyerols (DAG) were increased in the cerebral cortex of ALDH5A1 KO mice (Figure 6a).”
Quote in the paperSubstantial claim - Findingown data
Proteins of the GABAergic synapse, including both isoforms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD1 and GAD2) and the astrocytic GABA transporter GAT3, were dysregulated in the ALDH5A1 knockout brain.
“Proteins of the GABAergic synapse were dysregulated in the ALDH5A1 KO brain, including both isoforms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD1 & GAD2) and the astrocytic GABA transporter GAT3.”
Quote in the paperSubstantial claim - Findingown data
Multiple proteins related to myelination and oligodendrocyte function displayed dysregulated expression in the ALDH5A1 knockout brain.
“Multiple proteins related to myelination and oligodendrocyte function displayed dysregulated expression in the ALDH5A1 KO brain.”
Quote in the paperSubstantial claim - Findingcitation
The regional proteome substantiates a previous report of reduced expression of selected myelin-associated genes, lower myelin content, and myelin sheath thickness in the ALDH5A1 KO brain.
“Our regional proteome substantiates a previous report of reduced expression of selected myelin-associated genes, lower myelin content, and myelin sheath thickness in the ALDH5A1 KO brain (Donarum et al., 2006).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Donarum et al., 2006 source
- Findingown data
Glutamine levels are selectively reduced in the ALDH5A1 KO brain.
“glutamine levels were selectively reduced in the ALDH5A1 KO brain”
Quote in the paperNot a substantial claim - Findingown data
Metabolism of [U-13C]glutamine was increased in brain slices of ALDH5A1 KO mice.
“metabolism of [U-13 C]glutamine was increased in the brain slices of ALDH5A1 KO mice”
- Also stated in: § 4.2 | Cellular energy metabolism, neurotransmitter recycling, and astrocyte function · plain
“Increased oxidative glutamine metabolism in the ALDH5A1 knockout brain.”
Quote in the paperSubstantial claim - Also stated in: § 4.2 | Cellular energy metabolism, neurotransmitter recycling, and astrocyte function · plain
- Findingcitation
The ALDH5A1 KO proteome displays elevated GFAP expression in all regions examined.
“These findings align well with the proteome displaying elevated GFAP expression in all regions examined.”
Quote in the paperNot a substantial claim - Findingown data
First turn metabolism of [U-13C]glutamate was maintained in ALDH5A1 KO cerebral cortical slices.
“either M + 2 or M + 3 labeling (first turn metabolism), which was also maintained in the ALDH5A1 KO cerebral cortical slices.”
Quote in the paperSubstantial claim - Findingown data
Astrocyte energetics are impaired in the cerebral cortex of ALDH5A1 knockout mice.
“F I G U R E 3 Impaired astrocyte energetics in the cerebral cortex of ALDH5A1 knockout mice.”
Quote in the paperSubstantial claim - Interpretationown data
There is an elevated capacity for exogenous glutamine metabolism in the ALDH5A1 KO brain.
“These results suggest an elevated capacity for exogenous glutamine metabolism in the ALDH5A1 KO brain, perhaps as a compensatory mechanism of the overall reduced glutamine amounts (Table 1).”
Quote in the paperSubstantial claim - Interpretationown data
The paper provides evidence of astrocyte and oligodendrocyte dysfunction in SSADH deficiency.
“Here, we provide evidence of astrocyte and oligodendrocyte dysfunction in SSADH deficiency.”
Quote in the paperSubstantial claim - Premisecitation
The ALDH5A1 knockout mouse recapitulates several pathological hallmarks of SSADH deficiency including cerebral GABA accumulation and seizures.
“We applied a genetic mouse model of SSADH deficiency, the ALDH5A1 knockout (KO) mouse, recapitulating several pathological hallmarks including cerebral GABA accumulation and seizures (Gupta et al., 2003;Hogema et al., 2001).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data
The reduced [1,2-13C]acetate metabolism indicates lower metabolic activity of astrocytes in ALDH5A1 KO cerebral cortex.
“suggesting a lower metabolic activity of astrocytes.”
Quote in the paperSubstantial claim- Rests on an assumption: [1,2-13C]Acetate is primarily metabolized in astrocytes.
- Interpretationreasoning
Reduced glutamine levels in SSADH deficiency may relate to a lack of substrate, the carbon backbone of GABA, for astrocyte glutamine synthesis.
“suggesting that reduced glutamine levels in SSADH deficiency may simply relate to a lack of substrate, namely the carbon backbone of GABA.”
Quote in the paperNot a substantial claim- Rests on an assumption: In astrocytes, glutamate can be converted into glutamine by glutamine synthetase (GS).
- Interpretationreasoning
Increased [U-13C]glutamine metabolism likely reflects a compensatory increase in neuronal glutamine metabolism due to inadequate astrocyte supply.
“likely reflecting a compensatory increase in neuronal glutamine metabolism due to inadequate astrocyte supply.”
Quote in the paperNot a substantial claim- Rests on an assumption: [U-13C]Glutamine is converted into glutamate M+5 by phosphate-activated glutaminase (PAG) activity.
- Interpretationown data
The study's comprehensive analyses demonstrate a widespread and selective dysregulation of glial function in SSADH deficiency.
“Our comprehensive analyses, including regional proteomic analysis, stable isotope tracing and brain lipidomic analysis, demonstrate a widespread and selective dysregulation of glial function in SSADH deficiency.”
Quote in the paperSubstantial claim - Interpretationreasoning
SSADH deficiency involves critical dysfunction of both astrocytes and oligodendrocytes.
“suggesting critical dysfunction of both astrocytes and oligodendrocytes in SSADH deficiency.”
Quote in the paperSubstantial claim - Interpretationown data
Altered aspartate levels in SSADH deficiency do not functionally interfere with malate-aspartate shuttle activity.
“our finding of sustained oxidative glucose metabolism (see discussion below), in combination with unchanged protein levels of all components of the MAS (MDH1, MDH2, GOT1, GOT2, SLC25A12 & SLC25A11, Data S1), indicate that the altered aspartate levels in SSADH deficiency does not functionally interfere with MAS activity.”
Quote in the paperNot a substantial claim - Interpretationown data
Uptake capacity of exogenous glutamate is maintained in ALDH5A1 KO slices.
“Glutamate M + 5 was unaltered in the ALDH5A1 KO slices (Figure 4), suggesting a maintained uptake capacity of exogenous glutamate.”
Quote in the paperSubstantial claim - Interpretationreasoning
Increased ALAT expression and alanine amounts in the ALDH5A1 KO brain could serve as a compensatory pathway of ammonia fixation.
“The observed increase in ALAT expression and alanine amounts in the ALDH5A1 KO brain could serve as a compensatory pathway of ammonia fixation”
Quote in the paperNot a substantial claim - Interpretationown data
Astrocytes in the ALDH5A1 knockout brain showed reactive astrogliosis, indicated by elevated GFAP expression.
“Astrocytes were heavily affected in the ALDH5A1 KO brain, showing elevated expression of glial fibrillary acid protein (GFAP) indicative of reactive astrogliosis.”
Quote in the paperSubstantial claim- Rests on an assumption: Elevated expression of glial fibrillary acid protein (GFAP) is indicative of reactive astrogliosis.
- Interpretationreasoning
Severe disruptions of amino acid homeostasis in SSADH deficiency may result from a complex combination of perturbed synthesis, metabolism, and transport.
“Collectively, these observations suggest that the severe disruptions of amino acid homeostasis in SSADH deficiency may be the result of a complex combination of perturbed synthesis, metabolism, and transport.”
Quote in the paperSubstantial claim - Premisecitation
Hippocampal mitochondria of ALDH5A1 KO mice show lower electron transport chain activity.
“functional analyses of hippocampal mitochondria of ALDH5A1 KO mice showed lower activity of the electron transport chain (Sauer et al., 2007).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Sauer et al., 2007 source
- Interpretationown data
The dysregulation entails disrupted lipid composition suggesting faulty myelination.
“This entails aberrant protein expression particularly related to astrocyte and oligodendrocyte function, impaired astrocyte energy metabolism and disrupted lipid composition suggesting faulty myelination.”
Quote in the paperSubstantial claim - Interpretationown data
Glutamine uptake capacity is maintained in both cerebral cortex and hippocampus of ALDH5A1 KO mice.
“No change in glutamine M + 5 was observed (Figure 5), suggesting a maintained glutamine uptake capacity in both regions.”
Quote in the paperSubstantial claim - Interpretationreasoning
Unchanged oxidative glucose metabolism and maintained TCA cycle function in ALDH5A1 KO brain slices may be the combined result of an increased number of mitochondria operating at lower efficiency.
“Our results of unchanged oxidative glucose metabolism and maintained TCA cycle function in the brain slices of ALDH5A1 KO mice, may therefore be the combined result of an increased number of mitochondria operating at lower efficiency.”
Quote in the paperSubstantial claim - Interpretationown data
Dysfunctional neurotransmitter recycling in SSADH deficiency is mediated by altered metabolism rather than perturbed uptake capacity.
“Collectively, our results indicate that dysfunctional neurotransmitter recycling in SSADH deficiency are mediated by altered metabolism rather than perturbed uptake capacity.”
Quote in the paperSubstantial claim - Interpretationown data
The elevated capacity for exogenous glutamine metabolism may be a compensatory mechanism of the overall reduced glutamine amounts.
“These results suggest an elevated capacity for exogenous glutamine metabolism in the ALDH5A1 KO brain, perhaps as a compensatory mechanism of the overall reduced glutamine amounts (Table 1).”
Quote in the paperNot a substantial claim - Interpretationown data
Reduced expression of critical myelin-associated proteins alongside disrupted lipid profile suggests severe dysregulation or degeneration of myelin in ALDH5A1 KO mice.
“Collectively, our results of reduced expression of critical myelin-associated proteins, alongside the disrupted lipid profile, suggest severe dysregulation or degeneration of myelin in the ALDH5A1 KO mice.”
Quote in the paperSubstantial claim - Interpretationown data
Astrocyte and oligodendrocyte dysfunction is strongly associated with the pathology of SSADH deficiency.
“Our results demonstrate that astrocyte and oligodendrocyte dysfunction is strongly associated with the pathology of SSADH deficiency, warranting an exploration of glial cells as a therapeutic target in SSADH deficiency.”
Quote in the paperSubstantial claim - Premisecitation
When SSADH fails to convert succinic semialdehyde into succinate, GABA accumulates in the brain.
“When SSADH fails to convert succinic semialdehyde into succinate, GABA accumulates in the brain (Afshar-Saber et al., 2024;Gibson et al., 2002;Gupta et al., 2004;Hogema et al., 2001;Kirby, Walters, Brown, et al., 2020)”
Quote in the paperSubstantial claim0 of 3 sources checked - Interpretationown data
The dysregulation entails impaired astrocyte energy metabolism.
“This entails aberrant protein expression particularly related to astrocyte and oligodendrocyte function, impaired astrocyte energy metabolism and disrupted lipid composition suggesting faulty myelination.”
Quote in the paperSubstantial claim - Interpretationown data
Decreased oxidative metabolism in astrocytes in the ALDH5A1 KO mouse is definitively demonstrated by reduced 13C enrichment in TCA cycle metabolites from acetate.
“which we here extend to include several TCA cycle metabolites, definitively demonstrating decreased oxidative metabolism in astrocytes in the ALDH5A1 KO mouse.”
Quote in the paperSubstantial claim- Rests on an assumption: [1,2-13C]Acetate is primarily metabolized in astrocytes.
- Interpretationreasoning
Reduced expression of UGT8 and FA2H suggests a reduced capacity of myelin lipid synthesis in ALDH5A1 KO mice.
“The reduced expression of UGT8 and FA2H, proteins critical for HexCer and sulfatide synthesis, suggest a reduced capacity of myelin lipid synthesis.”
Quote in the paperSubstantial claim - Premisecitation
Brain TCA cycle intermediate levels are maintained in the ALDH5A1 KO brain.
“the levels of brain TCA cycle intermediates are maintained in the ALDH5A1 KO brain (Gibson et al., 2002)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Gibson et al., 2002 source
- Interpretationown data
The severely perturbed lipidomic profile of the ALDH5A1 knockout brain suggests a critical dysregulation of lipid homeostasis, particularly relating to myelination.
“The severely perturbed lipidomic profile of the ALDH5A1 KO brain suggests a critical dysregulation of lipids homeostasis in particular relating to myelination.”
Quote in the paperSubstantial claim - Interpretationown data
The depletion of several myelin-enriched lipids suggests a severe dysregulation or degeneration of myelin in the ALDH5A1 knockout brain.
“suggesting a severe dysregulation or degeneration of myelin.”
Quote in the paperSubstantial claim - Interpretationown data
The dysregulation entails aberrant protein expression particularly related to astrocyte and oligodendrocyte function.
“This entails aberrant protein expression particularly related to astrocyte and oligodendrocyte function, impaired astrocyte energy metabolism and disrupted lipid composition suggesting faulty myelination.”
Quote in the paperSubstantial claim
- May combine two claims. 18
- Classified as probably not a substantial claim. 6
- The quote only partly states this claim. 1
May combine two claims.
PremisecitationSSADH deficiency is caused by loss-of-function mutations in the SSADH enzyme, leading to impaired metabolism of the principal inhibitory neurotransmitter GABA.
“The cause of the disease is loss of function of the enzyme SSADH, leading to impaired metabolism of the principal inhibitory neurotransmitter GABA.”
- Also stated in: § 1 | INTRODUCTION · plain
“The most common disorder of GABA metabolism is SSADH deficiency, which can be caused by multiple loss-of-function mutations in the SSADH enzyme (Didiášová et al., 2020).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Didiášová et al., 2020 source
- Also stated in: § 1 | INTRODUCTION · plain
May combine two claims.
Findingown dataSome effects were restricted to specific brain regions, including selective reduction of astrocyte energy metabolism in cerebral cortex and perturbed hippocampal glutamate metabolism in ALDH5A1 KO hippocampus.
“Some effects were restricted to specific brain regions, including a selective reduction of astrocyte energy metabolism in the cerebral cortex and perturbed hippocampal glutamate metabolism in the ALDH5A1 KO hippocampus.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataIn total, 7615 protein groups were identified (cerebral cortex: 7481; hippocampus: 6948; cerebellum: 6079) with strong reproducibility between samples (Pearson correlation: 0.94-0.96).
“In total, we identified 7615 protein groups (cerebral cortex: 7481; hippocampus: 6948; cerebellum: 6079) (Figure S1A) with strong reproducibility between samples (Pearson correlation: 0.94-0.96).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSeveral protein changes overlapped between the cerebral cortex and hippocampus of ALDH5A1 KO mice (35 upregulated proteins and 45 down-regulated proteins), whereas the cerebellum displayed no individual overlap with these regions.
“In addition, several proteins changes overlapped between the cerebral cortex and hippocampus of ALDH5A1 KO mice (35 upregulated proteins and 45 down-regulated proteins), whereas the cerebellum displayed no individual overlap with these regions (Figure 1b).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenGlial protein expression, metabolism, and lipid homeostasis were all greatly affected in the ALDH5A1 KO brain.
“Glial protein expression, metabolism, and lipid homeostasis were all greatly affected in the ALDH5A1 KO brain.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataSeveral specific phospholipid species were elevated in the cerebral cortex of ALDH5A1 KO mice, indicating disrupted lipid metabolism.
“Several specific phospholipid species were elevated in the cerebral cortex of ALDH5A1 KO mice, indicating disrupted lipid metabolism.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataALDH5A1 KO mice show elevated expression of proteins related to L-serine synthesis and increased serine levels.
“We report elevated expression of proteins related to L-serine synthesis, coinciding with increased serine levels”
Quote in the paperNot a substantial claimThe quote only partly states this claim.
Findingown dataGABA accumulation was confirmed in the ALDH5A1 KO mouse model.
“which was confirmed in our mouse model.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data45% and 80% of all sulfatide species are reduced in the ALDH5A1 KO cerebral cortex and hippocampus, respectively.
“This was also the case for 45% and 80% of all sulfatide species in the ALDH5A1 KO cerebral cortex and hippocampus, respectively.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataALDH5A1 KO mice show increased cerebral aspartate levels, whereas previous studies reported unchanged aspartate amounts.
“Previous studies have reported unchanged aspartate amounts in the ALDH5A1 KO brain (Gibson et al., 2002;Gupta et al., 2004;Hogema et al., 2001), whereas we observed increased cerebral aspartate levels.”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
Findingown dataALDH5A1 KO mice show lower expression of the GABA synthesizing enzyme GAD and reduced GABA B receptor subunit GABBR2.
“We found lower expression of the GABA synthesizing enzyme GAD, together with reduced GABA B receptor subunit (GABBR2) expression in the ALDH5A1 KO mice.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataSeven proteins (GFAP, APOE, SLC7A5, OAT, CIRBP, MGST1, and SDHAF4) were upregulated in all three regions, whereas five proteins (ALDH5A1, MAG, ERMN, GSN, and PLEKHB1) were universally down-regulated in the ALDH5A1 KO brain.
“Of these, the expression of 7 proteins (GFAP, APOE, SLC7A5, OAT, CIRBP, MGST1, and SDHAF4) were upregulated in all three regions, whereas 5 proteins (ALDH5A1, MAG, ERMN, GSN, and PLEKHB1) were universally down-regulated in the ALDH5A1 KO brain.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe perturbed proteome in ALDH5A1 KO mice is supported by disrupted brain amino acid levels, impaired astrocyte metabolism, and altered lipid composition.
“The perturbed proteome was supported by disrupted brain amino acids levels, impaired astrocyte metabolism, and altered lipid composition of the ALDH5A1 KO mice”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe ALDH5A1 KO hippocampus displayed decreased expression of GLUL and GYS1, whereas PCX expression was elevated.
“including decreased expression of the astrocytic enzymes glutamine synthetase (GLUL) and glycogen synthase (GYS1), whereas pyruvate carboxylase (PCX) expression was elevated.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataSeveral astrocyte-specific proteins were dysregulated in ALDH5A1 KO mice, including upregulated GFAP and decreased PYGM.
“several astrocyte-specific proteins were dysregulated including upregulated expression of glial fibrillary acidic protein (GFAP), whereas glycogen phosphorylase (PYGM) expression was decreased.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn total, 169 proteins displayed increased expression, whereas 200 proteins showed lower expression in ALDH5A1 KO mice.
“In total, 169 proteins displayed increased expression, whereas 200 proteins showed lower expression in the ALDH5A1 KO mice.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningNo randomization was applied because two defined littermate groups (ALDH5A1 KO and wild-type) were used continuously for the experiments.
“No randomization was applied since two defined littermate groups (ALDH5A1 KO & wild-type) were used continuously for the experiments.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenInvestigators were blinded during sample analysis.
“Investigators were blinded during sample analysis.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataHexCer and ST are myelin-enriched sphingolipids, suggesting critical dysregulation of myelin lipids in ALDH5A1 KO brain.
“HexCer and ST are myelin-enriched sphingolipids suggesting a critical dysregulation of myelin lipids in the ALDH5A1 KO brain.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataGlutamate metabolism is selectively impaired in the ALDH5A1 KO hippocampus, whereas the cerebral cortex was unaffected.
“These results show that glutamate metabolism is selectively impaired in the ALDH5A1 KO hippocampus, whereas the cerebral cortex was unaffected.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenSample sizes were based on the variance of pilot studies and previous experiments.
“Sample sizes were based on the variance of pilot studies and previous experiments.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationGlutamine synthesis is the principal route of fixating ammonia in the brain.
“glutamine synthesis is also the principal route of fixating ammonia in the brain (Andersen & Schousboe, 2023a).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Andersen & Schousboe, 2023a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMyelin is comprised of 70%-80% lipids.
“As myelin is comprised of 70%-80% lipids (Schmitt et al., 2015), we finally sought to substantiate the dysregulated proteomic profile of myelination-related proteins in the ALDH5A1 KO mice (Figure 1c).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Schmitt et al., 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
May combine two claims.
Interpretationown dataThe proteome of the ALDH5A1 KO brain suggests a clear regional vulnerability of SSADH deficiency (hippocampus > cerebral cortex > > cerebellum) particularly affecting proteins related to amino acid homeostasis, energy metabolism, astrocyte function, and oligodendrocyte myelination.
“Collectively, the proteome of the ALDH5A1 KO brain suggest a clear regional vulnerability of SSADH deficiency (hippocampus > cerebral cortex > > cerebellum) particularly affecting proteins related to amino acid homeostasis, energy metabolism, astrocyte function, and oligodendrocyte myelination.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The irreversible metabolism of GABA is exclusively facilitated by GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH).
“the irreversible metabolism of GABA is exclusively facilitated by the two enzymes GABA-transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH).”
The paper relies on this without support.
The combined action of GABA-T and SSADH converts the GABA carbon backbone into the TCA intermediate succinate for further oxidation.
“The combined action of these enzymes converts the GABA carbon backbone into the tricarboxylic acid (TCA) intermediate succinate for further oxidation.”
The paper relies on this without support.
Glial metabolism and function remain poorly investigated in SSADH deficiency.
“Yet, glial metabolism and function remain poorly investigated in SSADH deficiency.”
The paper relies on this without support.
Astrocytes metabolize GABA and glutamate extensively to support glutamine synthesis, subsequently aiding to replenish the neuronal GABA and glutamate pools.
“Particularly astrocytes metabolize these two neurotransmitters extensively to support glutamine synthesis, subsequently aiding to replenish the neuronal GABA and glutamate pools.”
The paper relies on this without support.
[1,2-13C]Acetate is primarily metabolized in astrocytes.
“[1,2-13 C]Acetate is primarily metabolized in astrocytes, entering the TCA cycle as acetyl CoA M + 2 units”
The paper relies on this without support.
Cellular uptake of [U-13C]glutamate leads to M+5 enrichment of the intracellular glutamate pool, reflecting glutamate uptake.
“Cellular uptake of [U-13 C]glutamate leads to M + 5 enrichment of the intracellular glutamate pool reflecting glutamate uptake.”
The paper relies on this without support.
[U-13C]Glutamine is converted into glutamate M+5 by phosphate-activated glutaminase (PAG) activity.
“[U-13 C]Glutamine is converted into glutamate M + 5 by phosphate-activated glutaminase (PAG) activity”
The paper relies on this without support.
In astrocytes, glutamate can be converted into glutamine by glutamine synthetase (GS).
“In astrocytes, glutamate can be converted into glutamine by glutamine synthetase (GS).”
The paper relies on this without support.
Elevated expression of glial fibrillary acid protein (GFAP) is indicative of reactive astrogliosis.
“showing elevated expression of glial fibrillary acid protein (GFAP) indicative of reactive astrogliosis.”
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., Gable, A. L., Fang, T., Doncheva, N. T., Pyysalo, S., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkac1000 · Cited by 9,726 · see citing works
Krasemann, S., Madore, C., Cialic, R., Baufeld, C., Calcagno, N., El Fatimy, R., Beckers, L., O’Loughlin, E., Xu, Y., Fanek, Z., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.08.008 · Cited by 2,979 · see citing works
Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics
Matyash, V., Liebisch, G., Kurzchalia, T. V., Shevchenko, A., & Schwudke, D. (2008) · Journal of Lipid Research · doi:10.1194/jlr.d700041-jlr200 · Cited by 2,615 · see citing works
Reactive astrocyte nomenclature, definitions, and future directions
Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00783-4 · Cited by 2,533 · cited 1× · see citing works
“Astrocytes become reactive in SSADH deficiency (Brown, Gibson, et al., 2020; Hogema et al., 2001; Walters et al., 2021) leading to extensive cellular remodeling (Escartin et al., 2021; Patani et al., 2023).”
GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations
Ben-Ari, Y., Gaiarsa, J.-L., Tyzio, R., & Khazipov, R. (2007) · Physiological Reviews · doi:10.1152/physrev.00017.2006 · Cited by 1,304 · see citing works
Bak, L. K., Schousboe, A., & Waagepetersen, H. S. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03913.x · Cited by 1,114 · see citing works
Self-citationMyelination and support of axonal integrity by glia
Nave, K.-A. (2010) · Nature · doi:10.1038/nature09614 · Cited by 1,062 · see citing works
Brain Glucose Metabolism: Integration of Energetics with Function
Dienel, G. A. (2018) · Physiological Reviews · doi:10.1152/physrev.00062.2017 · Cited by 877 · see citing works
GABAergic Excitation Promotes Neuronal Differentiation in Adult Hippocampal Progenitor Cells
Tozuka, Y., Fukuda, S., Namba, T., Seki, T., & Hisatsune, T. (2005) · Neuron · doi:10.1016/j.neuron.2005.08.023 · Cited by 741 · see citing works
Function and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Mitophagy in human health, ageing and disease
Picca, A., Faitg, J., Auwerx, J., Ferrucci, L., & D’Amico, D. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00930-8 · Cited by 635 · see citing works
Felipo, V., & Butterworth, R. F. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00019-9 · Cited by 626 · see citing works
Selective vulnerability in neurodegenerative diseases
Fu, H., Hardy, J., & Duff, K. E. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0221-2 · Cited by 585 · see citing works
Astrocyte-neuron metabolic cooperation shapes brain activity
Bonvento, G., & Bolaños, J. P. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.006 · Cited by 580 · see citing works
Ultra‐high sensitivity mass spectrometry quantifies single‐cell proteome changes upon perturbation
Brunner, A., Thielert, M., Vasilopoulou, C., Ammar, C., Coscia, F., Mund, A., Hoerning, O. B., Bache, N., Apalategui, A., Lubeck, M., et al. (2022) · Molecular Systems Biology · doi:10.15252/msb.202110798 · Cited by 544 · see citing works
Functional roles of reactive astrocytes in neuroinflammation and neurodegeneration
Patani, R., Hardingham, G. E., & Liddelow, S. A. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00822-1 · Cited by 531 · see citing works
Lin, S.-C., & Bergles, D. (2004) · Nature Neuroscience · doi:10.1038/nn1162 · Cited by 449 · see citing works
Liu, X., Wang, Q., Haydar, T. F., & Bordey, A. (2005) · Nature Neuroscience · doi:10.1038/nn1522 · Cited by 446 · see citing works
Astrocytes in human central nervous system diseases: a frontier for new therapies
Verkhratsky, A., Butt, A., Li, B., Illes, P., Zorec, R., Semyanov, A., Tang, Y., & Sofroniew, M. V. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01628-9 · Cited by 428 · see citing works
A knowledge graph to interpret clinical proteomics data
Santos, A., Colaço, A. R., Nielsen, A. B., Niu, L., Strauss, M. T., Geyer, P. E., Coscia, F., Albrechtsen, N. J. W., Mundt, F. O., Jensen, L. J., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-021-01145-6 · Cited by 345 · see citing works
Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration.
Andersen, J. V., Markussen, K., Jakobsen, E., Schousboe, A., Waagepetersen, H., Rosenberg, P., & Aldana, B. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108719 · Cited by 331 · see citing works
Self-citationMcKenna, M. C., Waagepetersen, H. S., Schousboe, A., & Sonnewald, U. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.10.011 · Cited by 328 · see citing works
Self-citationAstrocytic Control of Biosynthesis and Turnover of the Neurotransmitters Glutamate and GABA
Schousboe, A., Bak, L. K., & Waagepetersen, H. S. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2013.00102 · Cited by 303 · see citing works
Self-citationMicroglial metabolic flexibility supports immune surveillance of the brain parenchyma
Bernier, L., York, E. M., Kamyabi, A., Choi, H. B., Weilinger, N. L., & MacVicar, B. A. (2020) · Nature Communications · doi:10.1038/s41467-020-15267-z · Cited by 302 · see citing works
Energy matters: presynaptic metabolism and the maintenance of synaptic transmission
Li, S., & Sheng, Z. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00535-8 · Cited by 273 · see citing works
Metabolism and functions of lipids in myelin
Schmitt, S., Cantuti‐Castelvetri, L., & Simons, M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.12.016 · Cited by 259 · see citing works
Andersen, J. V., Schousboe, A., & Verkhratsky, A. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102331 · Cited by 259 · see citing works
Self-citationGABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury
Zonouzi, M., Scafidi, J., Li, P., Mcellin, B. M., Edwards, J., Dupree, J. L., Harvey, L. D., Sun, D., Hübner, C. A., Cull-Candy, S. G., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3990 · Cited by 232 · see citing works
Sonnewald, U., Westergaard, N., Schousboe, A., Svendsen, J. S. M., Unsgård, G., & Petersen, S. B. (1993) · Neurochemistry International · doi:10.1016/0197-0186(93)90064-c · Cited by 224 · see citing works
Self-citationClinical spectrum of succinic semialdehyde dehydrogenase deficiency
Pearl, P. L., Gibson, K. M., Acosta, M. T., Vezina, L. G., Theodore, W. H., Rogawski, M. A., Novotny, E. J., Gropman, A. L., Conry, J. A., Berry, G. T., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000059549.70717.80 · Cited by 203 · see citing works
Uptake and metabolism of GABA in astrocytes cultured from dissociated mouse brain hemispheres
Schousboe, A., Hertz, L., & Svenneby, G. (1977) · Neurochemical Research · doi:10.1007/bf00964098 · Cited by 186 · see citing works
Self-citationJakobs, C., Bojasch, M., Mönch, E., Rating, D., Siemes, H., & Hanefeld, F. A. (1981) · Clinica Chimica Acta · doi:10.1016/0009-8981(81)90184-4 · Cited by 171 · see citing works
Peroxisomes, lipid metabolism and lipotoxicity
Wanders, R. J. A., Ferdinandusse, S., Brites, P., & Kemp, S. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2010.01.001 · Cited by 169 · see citing works
Loss-less Nano-fractionator for High Sensitivity, High Coverage Proteomics
Kulak, N. A., Geyer, P. E., & Mann, M. (2017) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o116.065136 · Cited by 167 · see citing works
Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase
Hogema, B. M., Gupta, M., Senephansiri, H., Burlingame, T. G., Taylor, M., Jakobs, C., Schutgens, R. B. H., Froestl, W., Snead, O. C., Diaz-Arrastia, R., et al. (2001) · Nature Genetics · doi:10.1038/ng727 · Cited by 157 · see citing works
Andersen, J. V., & Schousboe, A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15811 · Cited by 152 · see citing works
Self-citationOverview of myelin, major myelin lipids, and myelin-associated proteins
Kister, A. E., & Kister, I. (2023) · Frontiers in Chemistry · doi:10.3389/fchem.2022.1041961 · Cited by 148 · see citing works
Gibson, K. M., Christensen, E., Jakobs, C., Fowler, B., Clarke, M. A., Hammersen, G., Raab, K., Kobori, J. A., Moosa, A., Vollmer, B., et al. (1997) · PEDIATRICS · doi:10.1542/peds.99.4.567 · Cited by 140 · see citing works
Myelination of parvalbumin interneurons shapes the function of cortical sensory inhibitory circuits
Benamer, N., Vidal, M., Balia, M., & Angulo, M. C. (2020) · Nature Communications · doi:10.1038/s41467-020-18984-7 · Cited by 124 · see citing works
Endogenous GABA controls oligodendrocyte lineage cell number, myelination, and CNS internode length
Hamilton, N. B., Clarke, L. E., Arancibia‐Cárcamo, I. L., Kougioumtzidou, E., Matthey, M., Káradóttir, R. T., Whiteley, L., Bergersen, L. H., Richardson, W. D., & Attwell, D. (2016) · Glia · doi:10.1002/glia.23093 · Cited by 115 · see citing works
Gibson, K. M., Gupta, M., Pearl, P. L., Tuchman, M., Vezina, L. G., Snead, O. C., Smit, L. M. E., & Jakobs, C. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00113-6 · Cited by 113 · see citing works
Andersen, J. V., Westi, E. W., Jakobsen, E., Urruticoechea, N., Borges, K., & Aldana, B. I. (2021) · Molecular Brain · doi:10.1186/s13041-021-00842-2 · Cited by 89 · see citing works
Self-citationExpanding the function of oligodendrocytes to brain energy metabolism
Nave, K., Asadollahi, E., & Sasmita, A. O. (2023) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2023.102782 · Cited by 89 · see citing works
Glial Glutamine Homeostasis in Health and Disease
Andersen, J. V., & Schousboe, A. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03771-1 · Cited by 88 · see citing works
Self-citationGibson, K. M., Sweetman, L., Nyhan, W. L., Jakobs, C., Rating, D., Siemes, H., & Hanefeld, F. A. (1983) · Clinica Chimica Acta · doi:10.1016/0009-8981(83)90018-9 · Cited by 83 · see citing works
Kim, K., Pearl, P. L., Jensen, K., Snead, O. C., Malaspina, P., Jakobs, C., & Gibson, K. M. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3470 · Cited by 81 · see citing works
Gupta, M., Greven, R., Jansen, E. E. W., Jakobs, C., Hogema, B. M., Froestl, W., Snead, O. C., Bartels, H., Grompe, M., & Gibson, K. M. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.302.1.180 · Cited by 81 · see citing works
Defects in GABA metabolism affect selective autophagy pathways and are alleviated by mTOR inhibition
Lakhani, R., Vogel, K. R., Till, A., Liu, J., Burnett, S. F., Gibson, K. M., & Subramani, S. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303356 · Cited by 75 · see citing works
Malaspina, P., Roullet, J., Pearl, P. L., Ainslie, G. R., Vogel, K. R., & Gibson, K. M. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.06.009 · Cited by 73 · see citing works
CHEMICAL PATHOLOGY OF KRABBE'S DISEASE
Vanier, M. T., & Svennerholm, L. T. (1975) · Acta Paediatrica · doi:10.1111/j.1651-2227.1975.tb03896.x · Cited by 69 · see citing works
Cortez, M. A., Wu, Y., Gibson, K. M., & Snead, O. C. (2004) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2004.09.008 · Cited by 67 · see citing works
Myelin in Alzheimer’s disease: culprit or bystander?
Maitre, M., Jeltsch-David, H., Okechukwu, N. G., Klein, C., Patte-Mensah, C., & Mensah-Nyagan, A.-G. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01554-5 · Cited by 66 · see citing works
Succinic Semialdehyde Dehydrogenase Deficiency: GABAB receptor-mediated function
Buzzi, A., Wu, Y., Frantseva, M. V., Velázquez, J. L. P., Cortez, M. A., Liu, C. C., Shen, L. Q., Gibson, K. M., & Snead, O. C. (2006) · Brain Research · doi:10.1016/j.brainres.2006.02.131 · Cited by 62 · see citing works
Wu, Y., Buzzi, A., Frantseva, M. V., Perez-Velazquez, J. L., Cortez, M. A., Liu, C.-C., Shen, L., Gibson, K. M., & Snead, O. C. (2005) · Annals of Neurology · doi:10.1002/ana.20686 · Cited by 61 · see citing works
Gupta, M., Polinsky, M., Senephansiri, H., Snead, O. C., Jansen, E. E. W., Jakobs, C., & Gibson, K. M. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.04.008 · Cited by 56 · see citing works
Andersen, J. V., Jakobsen, E., Westi, E. W., Lie, M. E. K., Voss, C. M., Aldana, B. I., Schousboe, A., Wellendorph, P., Bak, L. K., Pinborg, L. H., et al. (2020) · Glia · doi:10.1002/glia.23872 · Cited by 56 · see citing works
Self-citationFocal neurometabolic alterations in mice deficient for succinate semialdehyde dehydrogenase
Gibson, K. M., Schor, D. S. M., Gupta, M., Guerand, W. S., Senephansiri, H., Burlingame, T. G., Bartels, H., Hogema, B. M., Bottiglieri, T., Froestl, W., et al. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00784.x · Cited by 55 · see citing works
Astrocytes regulate inhibitory neurotransmission through GABA uptake, metabolism, and recycling
Andersen, J. V., Schousboe, A., & Wellendorph, P. (2023) · Essays in Biochemistry · doi:10.1042/ebc20220208 · Cited by 55 · see citing works
Self-citationSuccinic Semialdehyde Dehydrogenase Deficiency: An Update
Didiasova, M., Banning, A., Brennenstuhl, H., Jung-Klawitter, S., Cinquemani, C., Opladen, T., & Tikkanen, R. (2020) · Cells · doi:10.3390/cells9020477 · Cited by 52 · see citing works
Dadsetan, S., Kukolj, E., Bak, L. K., Sørensen, M., Ott, P., Vilstrup, H., Schousboe, A., Keiding, S., & Waagepetersen, H. S. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.73 · Cited by 51 · see citing works
Self-citationChowdhury, G. M. I., Gupta, M., Gibson, K. M., Patel, A. B., & Behar, K. L. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04887.x · Cited by 50 · see citing works
Murine succinate semialdehyde dehydrogenase deficiency
Gupta, M., Hogema, B. M., Grompe, M., Bottiglieri, T. G., Concas, A., Biggio, G., Sogliano, C., Rigamonti, A. E., Pearl, P. L., Snead, O. C., et al. (2003) · Annals of Neurology · doi:10.1002/ana.10625 · Cited by 50 · see citing works
SAUER, S., KOLKER, S., HOFFMANN, G., TENBRINK, H., JAKOBS, C., GIBSON, K., & OKUN, J. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2006.12.009 · Cited by 50 · see citing works
Marian, O. C., Teo, J. D., Lee, J. Y., Song, H., Kwok, J. B., Landin-Romero, R., Halliday, G., & Don, A. S. (2023) · Acta Neuropathologica Communications · doi:10.1186/s40478-023-01544-7 · Cited by 50 · see citing works
Self-citationAstrocytes in selective vulnerability to neurodegenerative disease
Zimmer, T. S., Orr, A. L., & Orr, A. G. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.02.008 · Cited by 49 · see citing works
Jansen, E. E., Struys, E., Jakobs, C., Hager, E., Snead, O. C., & Gibson, K. M. (2008) · BMC Developmental Biology · doi:10.1186/1471-213x-8-112 · Cited by 41 · see citing works
Teo, J. D., Marian, O. C., Spiteri, A. G., Nicholson, M., Song, H., Khor, J. X. Y., McEwen, H. P., Ge, A., Sen, M. K., Piccio, L. M., et al. (2022) · Glia · doi:10.1002/glia.24329 · Cited by 40 · see citing works
Self-citationMcNair, L. F., Kornfelt, R., Walls, A. B., Andersen, J. V., Aldana, B. I., Nissen, J. D., Schousboe, A., & Waagepetersen, H. S. (2016) · Neurochemical Research · doi:10.1007/s11064-016-2116-5 · Cited by 39 · see citing works
Self-citationOligodendrocyte pathology in Huntington’s disease: from mechanisms to therapeutics
Bardile, C. F., Radulescu, C. I., & Pouladi, M. A. (2023) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2023.07.010 · Cited by 34 · see citing works
Andersen, J. V., Nissen, J. D., Christensen, S. K., Markussen, K. H., & Waagepetersen, H. S. (2017) · Neural Plasticity · doi:10.1155/2017/2107084 · Cited by 33 · see citing works
Self-citationDonarum, E. A., Stephan, D. A., Larkin, K., Murphy, E. J., Gupta, M., Senephansiri, H., Switzer, R. C., Pearl, P. L., Snead, O. C., Jakobs, C., et al. (2006) · Journal of Inherited Metabolic Disease · doi:10.1007/s10545-006-0247-6 · Cited by 27 · see citing works
Westi, E. W., Jakobsen, E., Voss, C. M., Bak, L. K., Pinborg, L. H., Aldana, B. I., & Andersen, J. V. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03053-5 · Cited by 26 · see citing works
Self-citationKirby, T., Walters, D. C., Brown, M., Jansen, E., Salomons, G. S., Turgeon, C., Rinaldo, P., Arning, E., Ashcraft, P., Bottiglieri, T., et al. (2020) · Metabolic Brain Disease · doi:10.1007/s11011-020-00550-1 · Cited by 24 · see citing works
Westi, E. W., Andersen, J. V., & Aldana, B. I. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106145 · Cited by 23 · see citing works
Self-citationBarceló‐Coblijn, G., Murphy, E. J., Mills, K. A., WINCHESTER, B. G., Jakobs, C., Snead, O. C., & Gibson, K. M. (2007) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2006.12.008 · Cited by 19 · see citing works
Saber, W. A., Teaney, N. A., Winden, K. D., Jumo, H., Shi, X., McGinty, G. E., Hubbs, J. L., Chen, C.-D., Latzer, I. T., Gasparoli, F. M., et al. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106386 · Cited by 18 · see citing works
Schreiber, J. M., Wiggs, E. A., Cuento, R., Norato, G., Dustin, I. H., Rolinski, R., Austermuehle, A., Zhou, X., Inati, S. K., Gibson, K. M., et al. (2021) · Journal of Child Neurology · doi:10.1177/08830738211012804 · Cited by 16 · see citing works
Walters, D. C., Lawrence, R., Kirby, T., Ahrendsen, J. T., Anderson, M. P., Roullet, J.-B., Murphy, E. J., Gibson, K. M., & the SSADH Deficiency Investigators Consortium (SDIC) (2021) · Journal of Child Neurology · doi:10.1177/0883073820987742 · Cited by 11 · see citing works
McNair, L. F., Andersen, J. V., & Waagepetersen, H. S. (2023) · Neurochemistry International · doi:10.1016/j.neuint.2023.105626 · Cited by 11 · see citing works
Self-citationBrown, M. N., Turgeon, C. T., Rinaldo, P., Pop, A., Salomons, G. S., Roullet, J., & Gibson, K. M. (2020) · JIMD Reports · doi:10.1002/jmd2.12075 · Cited by 10 · see citing works
The continuously evolving phenotype of succinic semialdehyde dehydrogenase deficiency
Juliá‐Palacios, N., Hübschmann, O. K., Olivella, M., Pons, R. M., Horvath, G. A., Lücke, T., Fung, C. W., Wong, S., Cortès‐Saladelafont, E., Rovira‐Remisa, M. M., et al. (2024) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12723 · Cited by 10 · see citing works
Peters, T. M. A., Engelke, U. F. H., de Boer, S., Reintjes, J. T. G., Roullet, J., Broekman, S., de Vrieze, E., van Wijk, E., Wamelink, M. M. C., Artuch, R., et al. (2024) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12657 · Cited by 7 · see citing works
Brown, M. N., Gibson, K. M., Schmidt, M. A., Walters, D. C., Arning, E., Bottiglieri, T., & Roullet, J. (2020) · JIMD Reports · doi:10.1002/jmd2.12151 · Cited by 6 · see citing works
Kirby, T. O., Walters, D. C., Shi, X., Turgeon, C. T., Rinaldo, P., Arning, E., Ashcraft, P., Bottiglieri, T., DiBacco, M. L., Pearl, P. L., et al. (2020) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-020-01522-5 · Cited by 6 · see citing works
Andersen, J. V., Westi, E. W., Griem‐Krey, N., Skotte, N. H., Schousboe, A., Aldana, B. I., & Wellendorph, P. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15814 · Cited by 6 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Glutamate/ GABA ‐Glutamine Cycle: Insights, Updates, and Advances
Andersen, J. V. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70029 · Cited by 156 · see citing works
Self-citationJoseph, G. U., Oyovwi, M. O., Jeroh, E., Esuku, D. T., & Ben‐Azu, B. (2025) · Journal of Molecular Pathology · doi:10.3390/jmp6020012 · Cited by 23 · see citing works
Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases
Shen, R., Sung, K., Ding, J., & Wu, C. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00543-7 · Cited by 6 · see citing works
Structural basis for selective inhibition of human GABA transporter GAT3
Mortensen, J. S., Bavo, F., Jensen, M. H., Pedersen, A. P. S., Storm, J. P., Pape, T., Frølund, B., Wellendorph, P., & Shahsavar, A. (2026) · Nature Communications · doi:10.1038/s41467-026-68479-0 · Cited by 3 · see citing works
Self-citationMcKenna, M. C., Sonnewald, U., Waageptersen, H. S., & White, H. S. (2024) · Journal of Neurochemistry · doi:10.1111/jnc.16207 · Cited by 2 · see citing works
Central Dysmyelination in SSADH‐Deficient Humans and Mice
Latzer, I. T., Lee, H. H. C., Yang, E., Alves, C., Bertoldi, M., Fung, C., Steele, S. V., Kule, M. E., Jin, Z., Rotenberg, A., et al. (2025) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.70148 · Cited by 2 · see citing works
Qian, L., Deng, Y., Song, M., Zhang, Z., Cheng, J., Zhu, B., Wu, M., Zhang, H., & Hu, Y. (2026) · Translational Neurodegeneration · doi:10.1186/s40035-026-00562-4 · Cited by 2 · see citing works
Wellendorph, P., Gauger, S. J., Andersen, J. V., Kornum, B. R., Solbak, S. M. Ø., & Frølund, B. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100064 · Cited by 1 · see citing works
Self-citationLi, Y., Li, Q., Wang, Y., Wang, X., Di, G., Niu, M., Xu, Z., & Huang, Y. (2026) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-026-01218-7 · Cited by 1 · see citing works
Kędracka–Krok, S., Nowak, J., Fic, E., Solich, J., Rybczyński, P., Romanska, W., Sarga, P., Pustelny, K., & Dziedzicka‐Wasylewska, M. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70229
Nehela, Y., & Killiny, N. (2026) · Plant Molecular Biology · doi:10.1007/s11103-025-01673-8
Liao, P., Zhang, L., Zhang, L., & Hu, Z. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03819-6
Koshu, K., Horiguchi, A., Mizuno, T., Aoki, S., Watanabe, M., Takino, N., Ito, M., Jimbo, E. F., Muramatsu, K., Muramatsu, S.-I., et al. (2026) · Molecular Therapy Advances · doi:10.1016/j.omta.2026.201860
- Authors
- Andersen, J. V., Marian, O. C., Qvist, F. L., Westi, E. W., Aldana, B. I., Schousboe, A., Don, A. S., Skotte, N. H., & Wellendorph, P.
- Affiliations
- University of Copenhagen (DK)
- The University of Sydney (AU)
- Corresponding author
- Andersen, Jens V.
- Wellendorph, Petrine
- ORCID
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2024-06-20
- Volume
- 72
- Issue
- 10
- Pages
- 1821-1839
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W4399858902
- Cited by
- 13
- References
- 86
- Citations by year
- 2026: 7 · 2025: 5 · 2024: 1
- FWCI
- 3.78
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Glia (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Funders
- Novo Nordisk Fonden (NNF21OC0067835)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- succinic semialdehyde dehydrogenase deficiency, GABA metabolism, astrocyte function, myelin degeneration, sphingolipids, glutamine metabolism, amino acid homeostasis, mitochondrial metabolism, hippocampus, cerebral cortex, neurometabolic disorders
- MeSH terms
- Amino Acid Metabolism, Inborn Errors, Animals, Astrocytes, Brain, Developmental Disabilities, gamma-Aminobutyric Acid, Mice, Inbred C57BL, Oligodendroglia, Mice, Knockout, Succinate-Semialdehyde Dehydrogenase, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-11-02.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-11-02.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
