ArticleThe American journal of psychiatry2008
Altered expression of genes involved in GABAergic transmission and neuromodulation of granule cell activity in the cerebellum of schizophrenia patients.
Article in The American journal of psychiatry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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49 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Pre-frontal parvalbumin interneurons in schizophrenia: a meta-analysis of post-mortem studies.Journal of neural transmission (Vienna, Austria : 1996) · 2019Pooled it
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- γ neuromodulations: unraveling biomarkers for neurological and psychiatric disorders.Military Medical Research · 2025Review
- The immediate alteration of cerebellar Glx/GABA and cerebello-thalamo-cortical connectivity in patients with schizophrenia after cerebellar TMS.Schizophrenia (Heidelberg, Germany) · 2025Article
- Manipulation of α4βδ GABABrain research · 2024Article
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- New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment.Frontiers in cellular neuroscience · 2024Review
- New Therapeutic Targets and Drugs for Schizophrenia Beyond Dopamine D2 Receptor Antagonists.Neuropsychiatric disease and treatment · 2024Review
- Why Can Modulation of α6-Containing GABAArchives of pharmacology and therapeutics · 2024Article
- Cerebellar Functional Dysconnectivity in Drug-Naïve Patients With First-Episode Schizophrenia.Schizophrenia bulletin · 2023Article
- Rare variants implicate NMDA receptor signaling and cerebellar gene networks in risk for bipolar disorder.Molecular psychiatry · 2022Article
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- Kainate Receptor-Mediated Depression of Glutamate Release Involves Protein Kinase A in the Cerebellum.International journal of molecular sciences · 2019Article
- Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia.Scientific reports · 2018Article
- Cerebellar αBritish journal of pharmacology · 2018Article
- Chromosomal Conformations and Epigenomic Regulation in Schizophrenia.Progress in molecular biology and translational science · 2018Review
- The effects of prenatal H1N1 infection at E16 on FMRP, glutamate, GABA, and reelin signaling systems in developing murine cerebellum.Journal of neuroscience research · 2017Article
- α4βδ GABANeuroscience · 2017Article
- State-dependent and -independent effects of dialyzing excitatory neuromodulator receptor antagonists into the ventral respiratory column.Journal of applied physiology (Bethesda, Md. : 1985) · 2017Article
- Metabotropic glutamate receptor 3 (mGlu3; mGluR3; GRM3) in schizophrenia: Antibody characterisation and a semi-quantitative western blot study.Schizophrenia research · 2016Article
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5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDeficits in gamma-aminobutyric acid (GABA) signaling have been described in the prefrontal cortex, limbic system, and cerebellum in individuals with schizophrenia. The purpose of the present study was to further investigate cerebellar gene expression alterations as they relate to decreases in GABAergic transmission by examining the expression of GABAergic markers, N-methyl-d-aspartic-acid (NMDA) receptor subunits, and cerebellum neuromodulators in individuals with schizophrenia.
methodSubjects were postmortem men with a diagnosis of schizophrenia (N=13) and a postmortem interval-matched non-psychiatric male comparison group (N=13). The authors utilized real-time-quantitative polymerase chain reaction (PCR) to measure mRNA levels of the following GABAergic markers: glutamic acid decarboxylase (GAD) 65 and 67; GABA plasma membrane transporter-1 (GAT-1); GABA type A (GABA(A)) receptor subunits alpha(6), beta(3), and delta; and parvalbumin. In addition, real-time-quantitative PCR was utilized to assess mRNA levels of the NMDA receptor (NR) subunits NR1, NR2-A, NR2-B, NR2-C, and NR2-D as well as the cerebellar neuromodulators glutamate receptor (GluR)-6, kainate-preferring glutamate receptor subunit-2 (KA2), metabotropic glutamate receptor (mGluR)-2 and mGluR3, and neuronal nitric oxide synthase. Measurements for mRNA levels were determined using lateral cerebellar hemisphere tissue from both schizophrenia and comparison subjects.
resultsSchizophrenia subjects showed significant decreases in mRNA levels of GAD(67), GAD(65), GAT-1, mGluR2, and neuronal nitric oxide synthase. Increases in GABA(A)-alpha(6 )and GABA(A)-delta as well as GluR6 and KA2 were also observed. Medication effects on the expression of the same genes were examined in rats treated with either haloperidol (Sprague-Dawley rats [N=16]) or clozapine (Long-Evans rats [N=20]). Both haloperidol and clozapine increased the levels of GAD(67) in the cerebellum and altered the expression of other cerebellar mRNAs.
conclusionsThese findings suggest that GABA transmission is decreased in the cerebellar cortices in individuals with schizophrenia and additional gene expression changes may reflect an attempt to increase GABA neurotransmission at the cerebellar glomerulus.
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