Alterations of Astrocytes in the Context of Schizophrenic Dementia.

Vadim V Tarasov,Vladimir N Chubarev,Cecil E Kirkland,Susanna S Sologova,Sergey O Bachurin,Gjumrakch Aliev,Siva G Somasundaram,Andrey A Svistunov,Polina Mukhortova,Dmitrii Levushkin

doi:10.3389/fphar.2019.01612

Abstract

The levels of the astrocyte markers (GFAP, S100B) were increased unevenly in patients with schizophrenia. Reactive astrogliosis was found in approximately 70% of patients with schizophrenia. The astrocytes play a major role in etiology and pathogenesis of schizophrenia. Astrocytes produce the components that altered in schizophrenia extracellular matrix system which are involved in inflammation, functioning of interneurons, glio-, and neurotransmitter system, especially glutamate system. Astrocytes activate the interneurons through glutamate release and ATP. Decreased expression of astrocyte glutamate transporters was observed in patients with schizophrenia. Astrocytes influence on N-methyl-d-aspartate (NMDA) receptors via D-serine, an agonist of the glycine-binding site of NMDA receptors, and kynurenic acid, an endogenous antagonist. NMDA receptors, on its turn, control the impulses of dopamine neurons. Therefore following theories of schizophrenia are proposed. They are a) activation of astrocytes for neuroinflammation, b) glutamate and dopamine theory, as astrocyte products control the activity of NMDA receptors, which influence on the dopamine neurons.

Highlights

Schizophrenia is a mental disorder, determined as a complex of positive, negative and cognitive symptoms (Carbon and Correll, 2014)
Disturbances in NMDA receptors in interneurons lead to the absence of inhibition impulses to the glutamate neurons, increasing glutamate activity especially in the prefrontal cortex, which can be related to negative symptoms of schizophrenia
As a result of our study, we can conclude that astrocytes allow us to look at the etiology and pathogenesis of schizophrenia from a new point of view

Summary

Alterations of Astrocytes in the Context of Schizophrenic Dementia

The levels of the astrocyte markers (GFAP, S100B) were increased unevenly in patients with schizophrenia. Reactive astrogliosis was found in approximately 70% of patients with schizophrenia. The astrocytes play a major role in etiology and pathogenesis of schizophrenia. Astrocytes produce the components that altered in schizophrenia extracellular matrix system which are involved in inflammation, functioning of interneurons, glio-, and neurotransmitter system, especially glutamate system. Astrocytes activate the interneurons through glutamate release and ATP. Decreased expression of astrocyte glutamate transporters was observed in patients with schizophrenia. They are a) activation of astrocytes for neuroinflammation, b) glutamate and dopamine theory, as astrocyte products control the activity of NMDA receptors, which influence on the dopamine neurons

INTRODUCTION

Evidences of Alterations in Astrocyte System in Different Brain Areas

CONCLUSION

Cognitive symptoms

Findings

AUTHOR CONTRIBUTIONS