Participation of histone H3K9 acetylation in respiratory nuclei in the 6-OHDA animal model of Parkinson's disease

• Grant number: 24/13494-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Bárbara Falquetto
• Grantee: Ketlin Scomparin da Silva
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 23/00980-7 - Epigenetic characterization in respiratory nuclei in the 6-OHDA animal model of Parkinson's disease, AP.R

Abstract

Parkinson's disease (PD) was initially described in 1817 by James Parkinson, who believed in the fast discovery of medicines that would intervene in the progression of the disease. Two centuries later, this bias has still not been fully addressed. Despite the notable progress in the study of the disease, there are still deficient clarified topics, such as the impact of PD on breathing, its epidemiology and possible treatments. In mice injected with 6-OHDA in the striatum - a drug that allows the development of a mimetic model of idiopathic PD - there is a loss of neurons in respiratory nuclei, such as rostral ventral respiratory group (rVRG) and pre-Botzinger (preBotC), and of chemosensitive neurons of the retrotrapezoid nucleus (RTN). This explains the respiratory symptoms observed in the disease. Studies have shown that oxidative stress is a major mechanism to justify these losses, but recently, epigenetics has become a strong candidate as an etiology of PD, such as post-translational histone changes. Therefore, in this project, we study the epigenetic modulation on neurons in the RTN, preBotC and rVRG respiratory nuclei of individuals affected by PD - 6-OHDA animal model -, focusing on the acetylation of histone H3K9. The expression of the protein tyrosine hydroxylase will be evaluated by immunohistochemistry of the substantia nigra compacta to confirm the PD model. In addition to the analysis of H3K9ac protein expression in respiratory nuclei by Western Blot for epigenetic evaluation.