Cited by 54Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Lack of Change in Markers of Presynaptic Terminal Abundance Alongside Subtle Reductions in Markers of Presynaptic Terminal Plasticity in Prefrontal Cortex of Schizophrenia Patients

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Fung, Samantha J., Sivagnanasundaram, Sinthuja, Weickert, Cynthia Shannon·2011·Biological Psychiatry

Abstract

Background Reduced synaptic connectivity in frontal cortex may contribute to schizophrenia symptoms. While altered messenger RNA (mRNA) and protein expression of various synaptic genes have been found, discrepancies between studies mean a generalizable synaptic pathology has not been identified.Methods We determined if mRNAs encoding presynaptic proteins enriched in inhibitory (vesicular gamma-aminobutyric acid transporter [VGAT] and complexin 1) and/or excitatory (vesicular glutamate transporter 1 [VGluT1] and complexin 2) terminals are altered in the dorsolateral prefrontal cortex of subjects with schizophrenia (n = 37 patients, n = 37 control subjects). We also measured mRNA expression of markers associated with synaptic plasticity/neurite outgrowth (growth associated protein 43 [GAP43] and neuronal navigators [NAVs] 1 and 2) and mRNAs of other synaptic-associated proteins previously implicated in schizophrenia: dysbindin and vesicle-associated membrane protein 1 (VAMP1) mRNAs using quantitative polymerase chain reaction.Results No significant changes in complexin 1, VGAT, complexin 2, VGluT1, dysbindin, NAV2, or VAMP1 mRNA expression were found; however, expression of mRNAs associated with plasticity/cytoskeletal modification (GAP43 and NAV1) was reduced in schizophrenia. Although dysbindin mRNA did not differ in schizophrenia compared with control subjects, dysbindin mRNA positively correlated with GAP43 and NAV1 in schizophrenia but not in control subjects, suggesting low levels of dysbindin may be linked to reduced plasticity in the disease state. No relationships between three dysbindin genetic polymorphisms previously associated with dysbindin mRNA levels were found.Conclusions A reduction in the plasticity of synaptic terminals supports the hypothesis that their reduced modifiability may contribute to neuropathology and working memory deficits in schizophrenia.

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Crossref · 10.1016/j.biopsych.2010.09.036

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Authors
Fung, S. J., Sivagnanasundaram, S., & Weickert, C. S.
Affiliations
UNSW Sydney (AU)
Corresponding author
Fung, Samantha J.
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2011-01
Volume
69
Issue
1
Pages
71-79
ISSN
0006-3223 (ISSN-L)
OpenAlex
W2022715985
Cited by
54
References
73
Citations by year
2024: 4 · 2023: 5 · 2022: 2 · 2021: 4 · 2020: 4 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 6 · 2012: 4
FWCI
3.05
Type
journal article
Language
en
Open access
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Schizophrenia Research Institute
  • New South Wales Health
  • Macquarie Group Foundation
  • Neuroscience Research Australia
  • University of New South Wales
  • National Health and Medical Research Council of Australia
  • National Institute of Alcohol Abuse and Alcoholism (R24AA012725)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
schizophrenia, presynaptic terminals, synaptic plasticity, dorsolateral prefrontal cortex, synaptic gene expression, dysbindin, GAP-43, complexin, vesicular transporters, VAMP1, working memory deficits, synaptic connectivity
MeSH terms
Dysbindin, Carrier Proteins, DNA Helicases, Humans, Microtubule-Associated Proteins, Nerve Growth Factors, Nerve Tissue Proteins, Neuronal Plasticity, Schizophrenia, Biomarkers, Gene Expression, Prefrontal Cortex, Presynaptic Terminals, GAP-43 Protein, Polymorphism, Single Nucleotide, Adaptor Proteins, Vesicular Transport, Dystrophin-Associated Proteins, Vesicular Inhibitory Amino Acid Transport Proteins, Vesicular Glutamate Transport Protein 1, Vesicle-Associated Membrane Protein 1

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