Markers of Glutamate Synaptic Transmission and Plasticity Are Increased in the Anterior Cingulate Cortex in Bipolar Disorder
Open accessAbstract
Background Cortical glutamate levels are elevated in bipolar disorder, but the interpretation of this increase is unclear because glutamate has metabolic as well as neurotransmitter roles. We investigated this by measuring vesicular glutamate transporter 1 (VGluT1) expression, which reflects activity at glutamate synapses. We also measured netrin-G1 and netrin-G2 messenger RNAs because these genes are involved in the formation and plasticity of glutamatergic connections.Methods Using quantitative polymerase chain reaction, we quantified transcripts for VGluT1, netrin-G1 (isoforms G1c, G1d, and G1f), and netrin-G2 in the anterior cingulate cortex from subjects with bipolar disorder (n = 34), schizophrenia (n = 35), and healthy control subjects (n = 35).Results Vesicular glutamate transporter 1, netrin-G2, and netrin-G1d and G1f were increased in bipolar disorder but not in schizophrenia. Netrin-G1c did not differ between groups. Netrin-G1c and netrin-G1f expression showed left-right asymmetries. Vesicular glutamate transporter 1 messenger RNA correlated with brain weight.Conclusions Increased VGluT1 expression is supportive of elevated glutamate neurotransmission in the anterior cingulate cortex in bipolar disorder. The netrin-G1 and netrin-G2 findings suggest there may be an underlying difference in the plasticity of the affected circuitry.
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NPTX1 could contribute to BD pathology by deregulation of glutamatergic synaptic transmission.
“NPTX1 could contribute to BD pathology by deregulation of glutamatergic synaptic transmission (Eastwood and Harrison 2010).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Eastwood and Harrison 2010
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- Authors
- Eastwood, S. L., & Harrison, P. J.
- Affiliations
- University of Oxford (GB)
- Corresponding author
- Harrison, Paul J.
- ORCID
- Harrison, Paul J.
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 67
- Issue
- 11
- Pages
- 1010-1016
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2868790
- OpenAlex
- W2142197455
- Cited by
- 122
- References
- 64
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 6 · 2023: 8 · 2022: 5 · 2021: 30 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 8 · 2015: 9 · 2014: 6 · 2013: 6 · 2012: 8
- FWCI
- 5.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- United Kingdom Medical Research Council
- Stanley Medical Research Institute
- GlaxoSmithKline
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, anterior cingulate cortex, glutamatergic neurotransmission, VGLUT1, synaptic plasticity, schizophrenia, gene expression, brain weight, hemispheric lateralization
- MeSH terms
- Netrins, Adult, Aged, Analysis of Variance, Bipolar Disorder, Female, Genotype, Glycoproteins, Gyrus Cinguli, Humans, Functional Laterality, Male, Middle Aged, Nerve Tissue Proteins, Synaptic Transmission, Neuronal Plasticity, Neurons, Schizophrenia, In Situ Hybridization, Presynaptic Terminals, Glutamic Acid, Reverse Transcriptase Polymerase Chain Reaction, Vesicular Glutamate Transport Protein 1, GPI-Linked Proteins
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