Beyond the γ-aminobutyric acid hypothesis of schizophrenia

Frontiers in Cellular Neuroscience

Neuroscience

Kazuyuki Fujihara¹ 

[1] Department of Psychiatry and Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan;Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine, Maebashi, Japan;

关键词: inhibitory neurons;    psychiatric disorders;    knockout rats;    genome editing;    microglia;   

DOI  :  10.3389/fncel.2023.1161608

 received in 2023-02-08, accepted in 2023-04-04,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Fujihara.