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Cited by 5Neuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental DisordersMemory and Neural Mechanisms

The DOI matches its Crossref record; 98 of the 98 references it cites were found in a registry or an index.

Impaired hippocampal plasticity associated with loss of recycling endosomal SLC9A6/NHE6 is ameliorated by the TrkB agonist 7,8-dihydroxyflavone

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Gao, Andy Y.L., Inglebert, Yanis, Shi, Roy, Ilie, Alina, Popic, Jelena, Mustian, Jamie, Sonenberg, Nahum, Orlowski, John, McKinney, R. Anne·2025·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DOI 10.1016/j.bbadis.2024.167529
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Abstract

exchanger isoform 6 (NHE6) are causal for Christianson syndrome (CS), a severe form of X-linked intellectual disability. NHE6 expression is also downregulated in other neurodevelopmental and neurodegenerative disorders, such as autism spectrum disorder and Alzheimer's disease, suggesting its dysfunction could contribute more broadly to the pathophysiology of other neurological conditions. To understand how ablation of NHE6 function leads to severe learning impairments, we assessed synaptic structure, function, and cellular mechanisms of learning in a novel line of Nhe6 knockout (KO) mice expressing a plasma membrane-tethered green fluorescent protein within hippocampal neurons. We uncovered significant reductions in dendritic spines density, AMPA receptor (AMPAR) expression, and AMPAR-mediated neurotransmission in CA1 pyramidal neurons. The neurons also failed to undergo functional and structural enhancement during long-term potentiation (LTP). Significantly, the selective TrkB agonist 7,8-dihydroxyflavone restored spine density as well as functional and structural LTP in KO neurons. TrkB activation thus may act as a potential clinical intervention to ameliorate cognitive deficits in CS and other neurodegenerative disorders.

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Crossref · 10.1016/j.bbadis.2024.167529

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Metadata

Authors
Gao, A. Y. L., Inglebert, Y., Shi, R., Ilie, A., Popic, J., Mustian, J., Sonenberg, N., Orlowski, J., & McKinney, R. A.
Affiliations
McGill University (CA)
Corresponding author
McKinney, R. Anne
ORCID
Venue
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
Publisher
Elsevier BV
Published
2025-01
Volume
1871
Issue
1
Pages
167529
ISSN
0925-4439 (ISSN-L)
DOI
10.1016/j.bbadis.2024.167529
OpenAlex
W4402899934
Semantic Scholar
855c107ec41b5445139813d627e18cbc7bf2ca61
Cited by
5
References
97
Citations by year
2026: 3 · 2025: 2
FWCI
0.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship@McGill (McGill) (submittedVersion, cc-by-nc-nd)
Funders
  • Institute of Neurosciences Mental Health and Addiction (MOP-133611)
  • Natural Sciences and Engineering Research Council of Canada (RGPIN 341942-13)
  • Canada First Research Excellence Fund
  • Canadian Institutes of Health Research
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
NHE6, SLC9A6, Christianson syndrome, X-linked intellectual disability, TrkB agonist, 7,8-dihydroxyflavone, hippocampal plasticity, dendritic spines, AMPA receptors, long-term potentiation, CA1 pyramidal neurons, synaptic plasticity, endosomal recycling, learning disabilities, neurodegenerative diseases
MeSH terms
Animals, Ataxia, Epilepsy, Hippocampus, Male, Intellectual Disability, Microcephaly, Synaptic Transmission, Neuronal Plasticity, Endosomes, Ocular Motility Disorders, Sodium-Hydrogen Exchangers, Receptors, AMPA, Mice, Knockout, Receptor, trkB, X-Linked Intellectual Disability, Genetic Diseases, X-Linked, Flavones, Dendritic Spines, Mice

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