Epigenetic characterization in respiratory nuclei in the 6-OHDA animal model of Parkinson's disease

• Grant number: 23/00980-7
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2024
• End date: September 30, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Bárbara Falquetto
• Grantee: Bárbara Falquetto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ana Carolina Takakura Moreira ; Thiago dos Santos Moreira
• Associated scholarship(s): 24/21499-8 - Trimethylation of histone H3K4 in the respiratory nuclei in the 6-OHDA animal model of Parkinsons Disease, BP.IC; 24/13496-9 - Epigenetic characterization of histone H3K27me3 in respiratory nuclei in the 6-OHDA animal model of Parkinson's disease, BP.IC; 24/13494-6 - Participation of histone H3K9 acetylation in respiratory nuclei in the 6-OHDA animal model of Parkinson's disease, BP.IC

Abstract

Parkinson's disease (PD) is a chronic and progressive idiopathic neurodegenerative disease. It is characterized by the death of dopaminergic neurons in the substantia nigra (SN) region, resulting from complex molecular interactions, such as epigenetic alterations, mitochondrial dysfunction, environmental toxins, and other cellular processes. Several studies correlate PD with respiratory alterations and neurodegeneration in the respiratory column (RC). Recently, epigenetics has become a strong candidate as an etiology of PD, such as the direct interaction of SIRT2 with histones and post-translational modifications. Therefore, we will evaluate the presence of histones H3K4me3, H3K9ac and H3K27me3 and SIR2 activity in CR in a 6-OHDA model of PD. For this, the PD model will be induced in male mice by bilateral injection of 6-OHDA in the striatum and we will perform the immunohistochemistry technique for tyrosine hydroxylase in SN and whole-body plethysmography to confirm the PD model. Immunofluorescence with double labeling for phox2b or DAPI and histones will be done, and the protein concentration of these histones will be evaluated by Western Blot, besides the evaluation of SIRT2 activity by ELISA in RC such as the nucleus of solitary tract (NTS), retrotrapezoid nucleus (RTN), rostral ventral respiratory group (rVRG) and preBotzinger Complex (preBotC). (AU)