Stress-Related Brain Neuroinflammation Impact in Depression: Role of the Corticotropin-Releasing Hormone System and P2X7 Receptor

Abstract

Depression and other psychiatric stress-related disorders are leading causes of disability worldwide. Up to date, treatments of mood disorders have limited success, most likely due to the multifactorial etiology of these conditions. Alterations in inflammatory processes have been identified as possible pathophysiological mechanisms in psychiatric conditions. Here, we review the main features of 2 systems involved in the control of these inflammatory pathways: the CRH system as a key regulator of the stress response and the ATP-gated ion-channel P2X7 receptor (P2X7R) involved in the control of immune functions. The pathophysiology of depression as a stress-related psychiatric disorder is depicted in terms of the impact of CRH and P2X7R function on inflammatory pathways in the brain. Understanding pathogenesis of affective disorders will lead to the development of therapies for treatment of depression and other stress-related diseases.

Keywords: Corticotropin-releasing hormone receptor signaling; Corticotropin-releasing hormone system pathophysiology; Depression; Neuroinflammation; P2X7 receptor; Stress.