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Involvement of TRPM2 channel in neurodegeneration and microglial activation in a Parkinson's Disease model induced by 6-hydroxydopamine

Grant number: 20/02109-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2020
Effective date (End): April 30, 2024
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal researcher:Luiz Roberto Giorgetti de Britto
Grantee:Ana Flávia Fernandes Ferreira
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Parkinson's Disease (PD) is the second most common neurodegenerative disease in elderly, bringing a great socioeconomic impact due to the growing population aging scenario. It is mainly characterized by the death of dopaminergic neurons of the substantia nigra pars compacta and the consequent loss of dopamine in the striatum, besides that cell death may occur after an inflammatory condition with the presence of microglial activation. The Melastatin 2 Transient Potential Receptor channel (TRPM2) is a calcium channel activated by oxidative stress, being target of studies that research mechanisms underling cell death. However, little is known about participation of TRPM2 in PD. Thus, despite several studies already published, its etiology is not fully elucidated, requiring research that seeks to fill these gaps and describe possible pharmacological targets. In this way, the objective of this work is to evaluate the contribution of TRPM2 in neurodegeneration and microglial activation in an animal model of PD. For this, wild mice and knockouts for TRPM2, homo and heterozygous, will be used. They will be submitted to stereotaxic surgery to receive 6-hydroxydopamine (6-OHDA). The cylinder and apomorphine rotation test will be performed to validate the model. Seven and twenty one days after the surgery, animals will be euthanized and their brains will be used to H2O2 measurement, immunohistochemistry, immunoblotting and PCR techniques, in which will be assess dopaminergic neurons, TRPM2, Akt/GSK-3²/Caspase-3 cell survival pathway and microglia (ex: Iba-1, iNOS and TMEM119). (AU)

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