Beyond the γ-aminobutyric acid hypothesis of schizophrenia
Abnormalities in the γ-aminobutyric acid (GABA) system have been reported in the postmortem brains of individuals with schizophrenia. In particular, the reduction of one of the GABA-synthesizing enzymes, the 67-kDa isoform of glutamate decarboxylase (GAD67), has garnered interest among researchers b...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1161608/full |
| _version_ | 1797840430010728448 |
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| author | Kazuyuki Fujihara Kazuyuki Fujihara |
| author_facet | Kazuyuki Fujihara Kazuyuki Fujihara |
| author_sort | Kazuyuki Fujihara |
| collection | DOAJ |
| description | Abnormalities in the γ-aminobutyric acid (GABA) system have been reported in the postmortem brains of individuals with schizophrenia. In particular, the reduction of one of the GABA-synthesizing enzymes, the 67-kDa isoform of glutamate decarboxylase (GAD67), has garnered interest among researchers because of its role in the formation of γ-oscillations and its potential involvement in the cognitive dysfunction observed in schizophrenia. Although several animal models have been generated to simulate the alterations observed in postmortem brain studies, they exhibit inconsistent behavioral phenotypes, leading to conflicting views regarding their contributions to the pathogenesis and manifestation of schizophrenia symptoms. For instance, GAD67 knockout rats (also known as Gad1 knockout rats) exhibit marked impairments in spatial working memory, but other model animals do not. In this review, we summarize the phenotypic attributes of these animal models and contemplate the potential for secondary modifications that may arise from the disruption of the GABAergic nervous system. |
| first_indexed | 2024-04-09T16:14:59Z |
| format | Article |
| id | doaj.art-b70b22497eeb4becad2dc862ab7a8a36 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-09T16:14:59Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-b70b22497eeb4becad2dc862ab7a8a362023-04-24T06:04:31ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-04-011710.3389/fncel.2023.11616081161608Beyond the γ-aminobutyric acid hypothesis of schizophreniaKazuyuki Fujihara0Kazuyuki Fujihara1Department of Psychiatry and Neuroscience, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, JapanAbnormalities in the γ-aminobutyric acid (GABA) system have been reported in the postmortem brains of individuals with schizophrenia. In particular, the reduction of one of the GABA-synthesizing enzymes, the 67-kDa isoform of glutamate decarboxylase (GAD67), has garnered interest among researchers because of its role in the formation of γ-oscillations and its potential involvement in the cognitive dysfunction observed in schizophrenia. Although several animal models have been generated to simulate the alterations observed in postmortem brain studies, they exhibit inconsistent behavioral phenotypes, leading to conflicting views regarding their contributions to the pathogenesis and manifestation of schizophrenia symptoms. For instance, GAD67 knockout rats (also known as Gad1 knockout rats) exhibit marked impairments in spatial working memory, but other model animals do not. In this review, we summarize the phenotypic attributes of these animal models and contemplate the potential for secondary modifications that may arise from the disruption of the GABAergic nervous system.https://www.frontiersin.org/articles/10.3389/fncel.2023.1161608/fullinhibitory neuronspsychiatric disordersknockout ratsgenome editingmicroglia |
| spellingShingle | Kazuyuki Fujihara Kazuyuki Fujihara Beyond the γ-aminobutyric acid hypothesis of schizophrenia Frontiers in Cellular Neuroscience inhibitory neurons psychiatric disorders knockout rats genome editing microglia |
| title | Beyond the γ-aminobutyric acid hypothesis of schizophrenia |
| title_full | Beyond the γ-aminobutyric acid hypothesis of schizophrenia |
| title_fullStr | Beyond the γ-aminobutyric acid hypothesis of schizophrenia |
| title_full_unstemmed | Beyond the γ-aminobutyric acid hypothesis of schizophrenia |
| title_short | Beyond the γ-aminobutyric acid hypothesis of schizophrenia |
| title_sort | beyond the γ aminobutyric acid hypothesis of schizophrenia |
| topic | inhibitory neurons psychiatric disorders knockout rats genome editing microglia |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1161608/full |
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