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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2020
• End date: April 30, 2025
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Ana Flávia Fernandes Ferreira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 22/14846-8 - TRPM2 knockout and its impact in an animal model of Parkinson's disease, BE.EP.DR

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)

Scientific publications

(8)

(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)

FIGUEROA, PAULINA BELEN SEPULVEDA; FERREIRA, ANA FLAVIA FERNANDES; BRITTO, LUIZ ROBERTO; DOUSSOULIN, ARLETTE PATRICIA; TORRAO, ANDREA DA SILVA. Association between thyroid function and Alzheimer's disease: A systematic review. METABOLIC BRAIN DISEASE, JUN 2021. (20/02109-3)

F. FERREIRA, ANA FLAVIA; G. BRITTO, LUIZ ROBERTO. The transient receptor potential melastatin 2: a new therapeutical target for Parkinson's disease?. NEURAL REGENERATION RESEARCH, v. 18, n. 8, p. 5-pg., 2023-08-01. (18/07366-4, 20/02109-3)

BIANCHETTI, MARIA E.; FERREIRA, ANA FLAVIA F.; BRITTO, LUIZ R. G.. Inhibition of neuroinflammation by GIBH-130 (AD-16) reduces neurodegeneration, motor deficits, and proinflammatory cytokines in a hemiparkinsonian model. FRONTIERS IN NEUROANATOMY, v. 18, p. 12-pg., 2024-12-16. (18/07366-4, 22/14846-8, 22/14820-9, 23/05618-4, 20/02109-3)

SINGULANI, MONIQUE PATRICIO; FERREIRA, ANA FLAVIA FERNANDES; FIGUEROA, PAULINA SEPULVEDA; CUYUL-VASQUEZ, IVAN; TALIB, LEDA LEME; BRITTO, LUIZ ROBERTO; FORLENZA, ORESTES VICENTE. Lithium and disease modification: A systematic review and meta-analysis in Alzheimer's and Parkinson's disease. AGEING RESEARCH REVIEWS, v. 95, p. 20-pg., 2024-02-24. (20/02109-3, 18/07366-4, 21/06378-1, 14/50873-3)

FERREIRA, ANA FLAVIA F.; ULRICH, HENNING; FENG, ZHONG-PING; SUN, HONG-SHUO; BRITTO, LUIZ ROBERTO. Neurodegeneration and glial morphological changes are both prevented by TRPM2 inhibition during the progression of a Parkinson's disease mouse model. Experimental Neurology, v. 377, p. 15-pg., 2024-04-25. (20/02109-3, 18/07366-4, 22/14820-9)

FIGUEROA, PAULINA BELEN SEPULVEDA; FERREIRA, ANA FLAVIA FERNANDES; BRITTO, LUIZ ROBERTO; DOUSSOULIN, ARLETTE PATRICIA; TORRAO, ANDREA DA SILVA. Association between thyroid function and Alzheimer's disease: A systematic review. METABOLIC BRAIN DISEASE, v. 36, n. 7, p. 1523-1543, OCT 2021. (20/02109-3)

FERNANDES FERREIRA, ANA FLAVIA; SINGULANI, MONIQUE PATRICIO; ULRICH, HENNING; FENG, ZHONG-PING; SUN, HONG-SHUO; BRITTO, LUIZ ROBERTO. Inhibition of TRPM2 by AG490 Is Neuroprotective in a Parkinson's Disease Animal Model. Molecular Neurobiology, JAN 2022. (18/07366-4, 20/02109-3)

FERREIRA, ANA FLAVIA F.; BINDA, KARINA HENRIQUE; REAL, CAROLINE CRISTIANO. The effects of treadmill exercise in animal models of Parkinson's disease: A systematic review. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 131, p. 1056-1075, DEC 2021. (18/25204-1, 20/02109-3)