Analysis of histone acetylation profiles in respiratory control regions in the MitoPark model of Parkinson's disease

• Grant number: 26/04176-6
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: August 21, 2026
• End date: August 20, 2027
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Takakura Moreira
• Grantee: Yasmin Cestari Aquino
• Supervisor: Anumantha Kanthasamy
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Georgia, Athens (UGA), United States
• Associated to the scholarship: 23/05415-6 - Analysis of respiratory activity and respiratory bulbar nuclei in the MitoPark mouse model of Parkinson's Disease, BP.DD

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). In addition to classic motor symptoms, PD patients present non-motor manifestations such as sleep disturbances and respiratory deficits, which remain poorly understood. Recent studies from our laboratory have shown that the genetic model of PD, the MitoPark mouse, exhibits reduced respiratory frequency, tidal volume, and minute ventilation under basal conditions from 16 to 30 weeks of age, as well as impaired ventilatory responses to hypercapnia and hypoxia. Neuroanatomical analyses demonstrated neuronal loss in key respiratory control nuclei in MitoPark mice, such as the pre-Bötzinger complex and the retrotrapezoid nucleus. Despite these findings, the molecular mechanisms underlying neurodegeneration in these respiratory nuclei have not yet been investigated. Thus, the objective of the present project is to characterize epigenetic alterations, specifically histone acetylation patterns, in key respiratory control regions of MitoPark mice and to determine their association with transcriptional changes and respiratory impairment. To this end, MitoPark and control animals at two distinct ages will be used to investigate acetylation profiles in the pre-Bötzinger complex and retrotrapezoid nucleus using the AcetylScan technique. The expression of enzymes involved in histone acetylation and deacetylation in respiratory regions will also be evaluated by immunofluorescence. Finally, RNA sequencing (RNA-seq) will be performed to determine potential transcriptional changes in respiratory regions of MitoPark mice. (AU)