Glial Purinergic Signaling-Mediated Oxidative Stress (GPOS) in Neuropsychiatric Disorders

Oxidative stress (OS) has been implicated in the progression of multiple neuropsychiatric disorders, including schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder, and autism. However, whether glial purinergic signaling interaction with oxidative/antioxidative system displays an important role in neuropsychiatric disorders is still unclear. In this review, we firstly summarize the oxidative/antioxidative pathways shared in different glial cells and highlight the cell type-specific difference in response to OS. Then, we collect the evidence showing the regulation of purinergic signaling in OS with an emphasis on adenosine and its receptors, P2Y1 receptor in the P2Y family and P2X7receptor in the P2X family. Available data shows that the activation of P1 receptors and P2X accelerates the OS; reversely, the activation of the P2Y family (P2Y1) causes protective effect against OS. Finally, we discuss current findings demonstrating the contribution of the purinergic signaling system to neuropsychiatric disorders and point out the potential role of OS in this process to propose a "glial purinergic-oxidative stress" ("GPOS") hypothesis for future development of therapeutic strategies against a variety of neuropsychiatric disorders.