Cited by 267Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Molecular Determinants of Dysregulated GABAergic Gene Expression in the Prefrontal Cortex of Subjects with Schizophrenia

Mellios, Nikolaos, Huang, Hsien-Sung, Baker, Stephen P., Galdzicka, Marzena, Ginns, Edward, Akbarian, Schahram·2009·Biological Psychiatry

DOI 10.1016/j.biopsych.2008.11.019

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Abstract

Background Prefrontal deficits in gamma-aminobutyric acid (GABA)ergic gene expression, including neuropeptide Y (NPY), somatostatin (SST), and parvalbumin (PV) messenger RNAs (mRNAs), have been reported for multiple schizophrenia cohorts. Preclinical models suggest that a subset of these GABAergic markers (NPY/SST) is regulated by brain-derived neurotrophic factor (BDNF), which in turn is under the inhibitory influence of small noncoding RNAs. However, it remains unclear if these mechanisms are important determinants for dysregulated NPY and SST expression in prefrontal cortex (PFC) of subjects with schizophrenia.Methods Using a postmortem case-control design, the association between BDNF protein, NPY/SST/PV mRNAs, and two BDNF-regulating microRNAs (miR-195 and miR-30a-5p) was determined in samples from the PFC of 20 schizophrenia and 20 control subjects. Complementary studies were conducted in cerebral cortex of mice subjected to antipsychotic treatment or a brain-specific ablation of the Bdnf gene.Results Subjects with schizophrenia showed deficits in NPY and PV mRNAs. Within-pair differences in BDNF protein levels showed strong positive correlations with NPY and SST and a robust inverse association with miR-195 levels, which in turn were not affected by antipsychotic treatment or genetic ablation of Bdnf.Conclusions Taken together, these results suggest that prefrontal deficits in a subset of GABAergic mRNAs, including NPY, are dependent on the regional supply of BDNF, which in turn is fine-tuned through a microRNA (miRNA)-mediated mechanism.

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Authors: Mellios, N., Huang, H.-S., Baker, S. P., Galdzicka, M., Ginns, E., & Akbarian, S.
Affiliations: University of Massachusetts Chan Medical School (US)
Corresponding author: Akbarian, Schahram
ORCID: Mellios, Nikolaos
Huang, Hsien-Sung
Baker, Stephen P.
Akbarian, Schahram
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2009-06
Volume: 65
Issue: 12
Pages: 1006-1014
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2008.11.019
OpenAlex: W1979089999
Cited by: 266
References: 47
Citations by year: 2026: 5 · 2025: 5 · 2024: 15 · 2023: 8 · 2022: 13 · 2021: 11 · 2020: 17 · 2019: 17 · 2018: 15 · 2017: 12 · 2016: 18 · 2015: 22 · 2014: 23 · 2013: 22 · 2012: 14
FWCI: 12.75
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
eScholarship@UMassChan (submittedVersion)
Funders: National Institute of Mental Health (R01MH081943, MH071476, MH081943, R01MH071476)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: schizophrenia, prefrontal cortex, neuropeptide Y, somatostatin, parvalbumin, brain-derived neurotrophic factor, miR-195, miR-30a-5p, microRNA regulation, antipsychotic drugs, BDNF knockout mice, postmortem brain
MeSH terms: Adult, Aged, Aged, 80 and over, Animals, Chromatin, gamma-Aminobutyric Acid, Gene Expression Regulation, Genotype, Humans, Immunoassay, Male, Mice, Inbred C57BL, Middle Aged, Neuropeptide Y, Parvalbumins, RNA, Schizophrenia, Somatostatin, Case-Control Studies, Prefrontal Cortex, Mice, Knockout, Brain-Derived Neurotrophic Factor, MicroRNAs, Immunoprecipitation, Mice, Young Adult

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Molecular Determinants of Dysregulated GABAergic Gene Expression in the Prefrontal Cortex of Subjects with Schizophrenia

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