ArticleMolecular psychiatry2018
GAD1 alternative transcripts and DNA methylation in human prefrontal cortex and hippocampus in brain development, schizophrenia.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 70 citations in OpenAlex.
- Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex.Translational psychiatry · 2023Trial
- Pursuing the elusive biosignature for suicide: a decennial update.Molecular psychiatry · 2026Review
- Unraveling the Genetic and Molecular Architecture of Autism Spectrum Disorder: Implications for Clinical Genetics and Genomic Diagnostics.International journal of molecular sciences · 2026Review
- Alterations in GABAergic Interneurons, Neuroinflammation, and Epigenetics: Potential Targets for Therapeutic Strategies in Schizophrenia.Current neuropharmacology · 2026Article
- Unraveling the neurotoxic mechanisms of tranexamic acid in epilepsy induction: a network toxicology and molecular docking approach.BMC medicine · 2026Article
- The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders.International journal of molecular sciences · 2025Review
- A Refined Approach to Isolate Interneurons for High-Validity Epigenetic Studies in Human Brain Tissue.Methods and protocols · 2025Article
- The Impact of Gut Microbiota Changes on Methotrexate-Induced Neurotoxicity in Developing Young Rats.Biomedicines · 2024Article
- Review
- Distinctive Patterns of 5-Methylcytosine and 5-Hydroxymethylcytosine in Schizophrenia.International journal of molecular sciences · 2024Review
- GABAergic dysfunction in postmortem dorsolateral prefrontal cortex: implications for cognitive deficits in schizophrenia and affective disorders.Frontiers in cellular neuroscience · 2024Review
- Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.Neurochemical research · 2023Article
- The left-lateralisation of citrate synthase activity in the anterior cingulate cortex of male violent suicide victims.European archives of psychiatry and clinical neuroscience · 2023Article
- Localization and Diagnostic Specificity of Glutamic Acid Decarboxylase Transcript Alterations in the Dorsolateral Prefrontal Cortex in Schizophrenia.Biological psychiatry · 2023Article
- Associations of psychiatric disease and ageing with FKBP5 expression converge on superficial layer neurons of the neocortex.Acta neuropathologica · 2023Article
- In individuals with Williams syndrome, dysregulation of methylation in non-coding regions of neuronal and oligodendrocyte DNA is associated with pathology and cortical development.Molecular psychiatry · 2023Article
- Review
- Antidepressant effects of cherry leaf decoction on a chronic unpredictable mild stress rat model based on the Glu/GABA-Gln metabolic loop.Metabolic brain disease · 2022Article
- The DNA Methylation in Neurological Diseases.Cells · 2022Review
- Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Genetic variations and adverse environmental events in utero or shortly after birth can lead to abnormal brain development and increased risk of schizophrenia. γ-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, plays a vital role in normal brain development. GABA synthesis is controlled by enzymes derived from two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce transcript isoforms. While the full-length GAD1 transcript (GAD67) has been implicated in the neuropathology of schizophrenia, the transcript structure of GAD1 in the human brain has not been fully characterized. In this study, with the use of RNA sequencing and PCR technologies, we report the discovery of 10 novel transcripts of GAD1 in the human brain. Expression levels of four novel GAD1 transcripts (8A, 8B, I80 and I86) showed a lifespan trajectory expression pattern that is anticorrelated with the expression of the full-length GAD1 transcript. In addition, methylation levels of two CpG loci within the putative GAD1 promoter were significantly associated with the schizophrenia-risk SNP rs3749034 and with the expression of GAD25 in dorsolateral prefrontal cortex (DLPFC). Moreover, schizophrenia patients who had completed suicide and/or were positive for nicotine exposure had significantly higher full-length GAD1 expression in the DLPFC. Alternative splicing of GAD1 and epigenetic state appear to play roles in the developmental profile of GAD1 expression and may contribute to GABA dysfunction in the PFC and hippocampus of patients with schizophrenia.
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