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

• Grant number: 18/24140-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2019
• End date: October 05, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sabrina Francesca de Souza Lisboa
• Grantee: Nima Sanadgol
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/19731-6 - Identification of epigenetic mechanisms induced by stress which modulate endocannabinoid signaling and neuroimmunological mechanisms as new therapeutic targets to treat the posttraumatic stress disorder (PTSD), AP.JP

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.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANADGOL, NIMA; FERIZ, ADIB MIRAKI; LISBOA, SABRINA F.; JOCA, SAMIA R. L.. Putative role of glial cells in treatment resistance depression: An updated critical literation review and evaluation of single-nuclei transcriptomics data. Life Sciences, v. 331, p. 12-pg., 2023-08-28. (17/24304-0, 18/24140-0, 17/19731-6)