THE ROLE OF KETONE BODIES IN NEUROGENESIS AND NEUROPROTECTION IN MURINE MODEL OF PARKISONS DISEASE

• Grant number: 25/05124-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: July 01, 2025
• End date: February 28, 2029
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Carolina Takakura Moreira
• Grantee: Thayná Domingues Oliveira
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized mainly by the loss of dopaminergic neurons in the substantia nigra (SNpc). PD mainly affects motor control, promoting classic symptoms such as tremor, bradykinesia (slowness of movement), muscle rigidity, and postural instability. However, there are also a series of non-classical changes, including respiratory disorders. Most treatments aim to improve the classic symptoms of PD, like levodopa. However non-classical symptoms still require pharmacological alternatives. Adopting a ketogenic diet can increase plasma levels of ¿-hydroxybutyrate (¿OHB) to 4-5 mmol/L, which has neuroprotective effects in diseases such as Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis. Studies indicate that the increase in ketone bodies levels stimulates neurogenesis and offers protection against neurotoxins, such as 6-hydroxydopamine (6-OHDA), in Parkinson's models, reinforcing its therapeutic potential in neurodegenerative diseases. Ketone bodies, such as ¿OHB, help improve mitochondrial metabolism, in addition to reducing oxidative stress and increasing the efficiency of antioxidant mechanisms. Therefore, the present study aims to investigate whether treatment with ketone bodies will be able to prevent respiratory deficits and promote neuroprotection and neurogenesis in medullary nuclei that control breathing in a murine model of PD, induced by bilateral injection of 6-OHDA toxin into the striatum. (AU)