Neuromorphological Aspects of the GABAergic Hypothesis of the Pathogenesis of Schizophrenia
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Neuromorphological Aspects of the GABAergic Hypothesis of the Pathogenesis of Schizophrenia V. M. Vostrikov* Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 119, No. 8, Iss. 1, pp. 124–129, August, 2019. Original article received January 12, 2018. Accepted April 4, 2019. The scientific literature contains several hypotheses for the pathogenesis of schizophrenia. The most widespread hypotheses for schizophrenia are the dopaminergic, serotoninergic, and glutamatergic hypotheses. There is also the suggestion that other neurochemical systems are involved in the pathogenesis of schizophrenia, particularly the GABAergic. This review considers published data on derangements of GABAergic interneurons in schizophrenia, taking account of data on post-mortem, neuroimaging, molecular-genetic, and electrophysiological research. A hypothesis for the pathogenesis of schizophrenia based on impairments to the myelination of GABAergic interneurons is proposed, these impairments leading to decreases in the numbers of intra- and interhemisphere coherent connections and the appearance of symptoms of the disease. Keywords: schizophrenia, GABAergic interneurons, myelination, oligodendrocytes.
Introduction. Schizophrenia is one of the most severe mental disorders, whose etiology and pathogenesis – despite intense research by experts in many countries over many years – remain insufficiently studied [1]. Many hypotheses for the pathogenesis of schizophrenia have been proposed, and these are dominated by biological hypotheses (genetic, biochemical, immunological, brain development-related, etc.). The best developed among these are the dopaminergic, serotoninergic, glutamatergic, and receptor-neurochemical hypotheses [2–5]. Other neurochemical systems have also been suggested to be involved in the pathogenesis of schizophrenia, particularly the GABAergic [6, 7]. One feature of the current stage of development of these studies is that each individual hypothesis considers possible impairments to intercellular connections, taking cognizance of the state of myelination processes and the functions of oligodendrocytes [8]. In contrast to the dopaminergic and other neurochemical hypotheses of schizophrenia, the GABAergic concept has received less study in relation to its neuromorphological aspect. The data presented in this review reflect attempts to fill this gap by summarizing scientific research results in this area.
The GABAergic System of the Brain. The GABAergic system is the totality of nerve cells, fibers, and synapses synthesizing and releasing γ-aminobutyric acid (GABA) as transmitter. In the cerebral cortex, GABAergic nonpyramidal interneurons make up about 20% of all neurons and constitute a heterogeneous group of cells [9]. Cortical GABAergic interneurons play a key role in connecting pyramidal neurons in radial structures, i.e., microcolumns, and using them to build functionally plastic modules. GABAergic interneurons also play a fundamental role in the maturation of neural networks during postnatal devel
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