P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes

Abstract

The increasing prevalence of depression and diabetes mellitus has become a major public health problem worldwide. Studies have shown that people with diabetes are at a high risk of being diagnosed with depression, and diabetes complicates depression treatment by promoting the deterioration of glycemic control, reducing self-care ability and quality of life, and causing severe functional disability and early mortality. Moreover, health deterioration dramatically increases the financial cost of social and health care system. Thus, how to treat depression, diabetes, and diabetes complicated by depression has become one of the world's urgent concerns. The activation of nod-like receptor family pyrin domain containing 3 (NLRP3) is closely related to mental illness. This finding provides a new perspective for studying depression. NLRP3 plays an important role in the development of diabetes. In this review, we elaborate the definition and epidemiology of depression, diabetes, and diabetic depression and introduce the functional characteristics of an NLRP3 inflammasome and upstream P2X7 receptor. Moreover, related research on NLRP3 inflammasomes and P2X7 receptors is summarized and used as a reference for confirming that the excessive activation of P2X7-NLRP3 leads to the increased release of inflammatory cytokines, such as IL-1β, in depression and diabetes. We provide insights into the P2X7-NLRP3-IL-1β pathway as an important pathological mechanism and novel therapeutic target in diabetes and depression. Given that the P2X7-NLRP3-IL-1β pathway may play an important role in diabetes confounded by comorbid depression, the possibility of intervention with baicalin is proposed.

P2X7R-mediated Autophagic Impairment Contributes to Central Sensitization in a chronic Migraine Model with Recurrent Nitroglycerin Stimulation in Mice

“…on the activation of microglia and the NLRP3 in ammasome in the mice model of CM, which was consistent with the results of other neurological diseases reported previously by other teams [89][90][91][92].…”

Loganin Attenuates High Glucose-Induced Schwann Cells Pyroptosis by Inhibiting ROS Generation and NLRP3 Inflammasome Activation

“…P2RX7 stimulation represents the second signal to inflammasome activation by triggering K + efflux, as ATP-induced P2RX7 activation causes a sustained increase in intracellular Ca 2+ , inflammasome assembly and subsequent caspase-1 activation [ 59 , 60 ]. Excessive activation of P2RX7 and NLRP3 leads to increased inflammatory cytokine secretion, such as IL-1β in depression and diabetes [ 61 ]. Colomar et al pointed out that the maturation and release of interleukin 1β is required to stimulate P2RX7 in lipopolysaccharide-primed mouse Schwann cells [ 38 ].…”

α-Cyperone Confers Antidepressant-Like Effects in Mice via Neuroplasticity Enhancement by SIRT3/ROS Mediated NLRP3 Inflammasome Deactivation

“…Classical antidepressants such as paroxetine, amitriptyline and agomelatine were reported to reduce NLRP3, IL-1β, and IL-18 levels in patients with MDD ( Alcocer-Gomez et al, 2017 ). Chronic stress promoted the production of NLRP3 inflammasome contents and inflammatory cytokine IL-1β and IL-18 ( Wang et al, 2020 ). Compared with wild-type mice, NLRP3 gene knockout mice didn’t exhibit depression-like behaviors in SPT or TST after 4 weeks of CUMS exposure; meanwhile, NLRP3 gene knockout prevented the promotion of IL-1β in serum and hippocampi of CUMS mice ( Su et al, 2017 ).…”