Therapeutic effect of irisin in a model of Parkinsons disease induced by 6-hydroxydopamine

• Grant number: 23/02355-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Nicole Miki Kamidai
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The transmembrane protein FNDC5 - expressed in skeletal muscles, heart and brain - when cleaved, releases the irisin peptide responsible for mediating some of the beneficial effects promoted by physical activity. Recent studies have shown that irisin is capable of rescuing the synaptic plasticity of the hippocampus and exerting a neuroprotective role in a model of Alzheimer's disease. Among the neurodegenerative diseases, Parkinson's disease (PD) is listed as the second most commonly found in the elderly, being characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. This loss of dopaminergic neurons implies a reduction in dopamine release, resulting in a range of motor and non-motor symptoms. The exact cause for the onset of PD remains uncertain, and the available treatment considered the gold standard for PD - levodopa - when used in the long term can cause side effects. Thus, several studies seek a better understanding of the pathophysiological mechanisms involved in PD and possible therapeutic approaches. Preliminary studies in our laboratory showed promising results regarding intracerebroventricular irisin injection as a neuroprotective strategy in a model of PD induced by 6-hydroxydopamine (6-OHDA) in rats. In the present study, we will seek to assess whether irisin is capable of exerting a therapeutic effect using the model of PD induced by 6-OHDA in rats. For this purpose, behavioral tests and immunohistochemical techniques will be performed.