Astrocytic Regulation of Glutamate Transmission in Schizophrenia

Frontiers in Psychiatry

Dong Chuan Wu¹  Yu-Ying Mei¹  Ning Zhou¹ 

[1] Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan;Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan;

关键词: schizophrenia;    glutamate;    NMDA receptors;    excitatory amino acid transporters;    glutamate-glutamine cycle;    D-serine;   

DOI  :  10.3389/fpsyt.2018.00544

来源: DOAJ

【 摘 要 】

According to the glutamate hypothesis of schizophrenia, the abnormality of glutamate transmission induced by hypofunction of NMDA receptors (NMDARs) is causally associated with the positive and negative symptoms of schizophrenia. However, the underlying mechanisms responsible for the changes in glutamate transmission in schizophrenia are not fully understood. Astrocytes, the major regulatory glia in the brain, modulate not only glutamate metabolism but also glutamate transmission. Here we review the recent progress in understanding the role of astrocytes in schizophrenia. We focus on the astrocytic mechanisms of (i) glutamate synthesis via the glutamate-glutamine cycle, (ii) glutamate clearance by excitatory amino acid transporters (EAATs), (iii) D-serine release to activate NMDARs, and (iv) glutamatergic target engagement biomarkers. Abnormality in these processes is highly correlated with schizophrenia phenotypes. These findings will shed light upon further investigation of pathogenesis as well as improvement of biomarkers and therapies for schizophrenia.

【 授权许可】

Unknown