Evaluation of P2X7-induced inflammasome activation and microglia M1/M2 polarization in an animal model of treatment-resistant depression

Abstract

Around 30-60% of patients treated with routine antidepressant medications fail to achieve effectively remission of depressive symptoms leading to treatment resistant depression (TRD). In this condition, augmentation therapy such as adding of a mood stabiliser (such as lamotrigine or lithium) or an antipsychotic (such as olanzapine, quetiapine or risperidone) to an existing antidepressant treatments is often used. There is an essential need to precise description of cell and molecular mechanisms involved in the major depressive disorder (MDD), which could be highly applicable for introducing new curative treatments and decreasing rate of TRD. Recently a large body of evidence supports that the purinergic type 2X7 (P2X7) receptor activation in microglia cells and consequent activation of NLPR3 inflammasome have a critical role in the response to the antidepressant therapeutics. In this leading project we will investigate the effects of P2X7 receptor antagonist (A-804598) and inflammasome inhibition (CP-456,773), on microglia M1 and M2 polarization, inflammasome activation and neuroplasticity in the adrenocorticotropic hormone (ACTH)-induced animal model of TRD.