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Evaluation of the endocannabinoid signalling and cannabidiol effects on immunological parameters in a psychopathological mouse model of trait anxiety

Grant number: 18/17387-9
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): September 30, 2018
Effective date (End): September 29, 2019
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Francisco Silveira Guimaraes
Grantee:Alice Hartmann dos Santos
Supervisor abroad: Carsten T. Wotjak
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Local de pesquisa : Max Planck Society, Munich, Germany  
Associated to the scholarship:16/14282-6 - Evaluation of the cannabidiol effects under neuroimmunoendocrine and behavioral alterations induced by stress in mice, BP.DR

Abstract

Pathological anxiety is a common mental disorder that involves neuroendocrine, neuroanatomical, neuroimmune and neurotransmitter alterations. Anxiety disorders are highly correlated with other mental disorders such as depression and PTSD, in which the involvement of pro-inflammatory cytokines is better characterized and understood. Among these mediators, interleukin-1² (IL-1²) is widely described as a neuroinflammatory and antineurogenic agent, and induces anxiety- and depressive-like behaviors in experimental animals. The NLRP3 inflammasome (a cytosolic multiprotein complex activated in response to tissue damage, cellular metabolism alterations and infections) mediates most of the IL-1² effects, leading to activation of the innate immune system and, ultimately, inflammation. The NLRP3 inflammasome activation has been widely described in animal models of mental disorders, such as depression. The endocannabinoid system (ECB) is considered a stress-buffer system and induces immunomodulatory activity. Its recruitment usually induces anti-stress-, anxiolytic- and antidepressant-like effects. Cannabidiol (CBD), a non-psychotomimetic compound of Cannabis sativa, has shown antidepressant- and anxiolytic-like in animal models, as well as anti-inflammatory activity. The mechanisms of these effects are not entirely clear,but seems to involve, in addition to the ECB system, other molecular targets. The lineage of high- and normal-anxiety behavior mice (HAB/NAB) were developed through selective breeding to obtain a genetic mouse model of anxiety and depression. The HAB mice display several cognitive dysfunctions and anxiogenic- and depressive-like behaviors when compared to NAB mice. Although some mitochondrial dysfunction was already described in these mice, their immunological and cytokines profile, particularly changes in the NLRP3 inflammasome, have not been investigated until now. In this way, this project aims to assess the immunological profile of the HAB/NAB mice. Furthermore, we plan to verify if acute treatment with CBD or URB597, a drug that enhances the ECB signaling, can ameliorate some of the altered behavior observed in HAB mice. We also intend to verify is there is involvement of immune factors in these effects, specifically of the NLRP3 inflammasome.

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