Exploring molecular targets in the mesocorticolimbic system of rats subjected to deprivation chronic sleep concomitant with statin treatment

• Grant number: 25/05513-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: José de Anchieta de Castro e Horta Júnior
• Grantee: Gabriela Larissa Lima da Silva
• Supervisor: Ana Maria Ferreira de Sousa Sebastiao
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Universidade de Lisboa, Portugal
• Associated to the scholarship: 22/16417-7 - Action of statins on cognitive impairment induced by sleep deprivation in rats, BP.DR

Abstract

Chronic sleep deprivation constitutes a silent pandemic, affecting a large portion of the population and being associated with cognitive impairments, increased risk of cardiovascular and metabolic diseases, and mental disorders. At the same time, the prevalence of dyslipidemias has driven the clinical use of statins, drugs widely prescribed for the control of hyperlipidemia. In addition to their main action of inhibiting the enzyme HmgCoA reductase and reducing cholesterol levels, statins demonstrate pleiotropic effects, including neuroprotective properties that can mitigate cognitive impairments resulting from factors such as sleep deprivation. This study investigates the effects of different classes of statins - specifically, rosuvastatin, atorvastatin, and simvastatin - on the cognition of Wistar rats subjected to a chronic sleep deprivation protocol. The material to be analyzed in this project comes from a doctoral project in Brazil supported by FAPESP (Process 2022/16417-7). The animals were distributed into the following experimental groups: control group (CG) without sleep deprivation and treated with vehicle; sleep deprivation group (GP), with a maximum of 6 hours of sleep per day, using the adapted multiple platform method for inducing sleep deprivation and treated with vehicle; sleep deprivation groups associated with rosuvastatin, which received a single daily dose of 2.1 mg/kg (GPR-) and 20mg/kg (GPR+) of the drug; sleep deprivation groups associated with atorvastatin, which received a single daily dose of 4.2 mg/kg (GPA-) and 20mg/kg (GPA+) of the drug; sleep deprivation groups associated with simvastatin, which will receive a single daily dose of 4.2 mg/kg (GPS-) and 20 mg/kg (GPS+). Sleep deprivation and drug administration were performed concomitantly from the 75th day of postnatal life, lasting 45 days. Biological samples of brain tissue from all experimental groups will be used, previously collected fresh after decapitation, preserved in a freezer at -80 ºC and transported under strictly controlled conditions, in accordance with international guidelines, to ensure their integrity. Molecular changes will be assessed using techniques such as RNA-sequencing, RT-qPCR and Western Blotting, focusing on regions of the mesocorticolimbic circuit, such as the hippocampus, prefrontal cortex, nucleus accumbens and amygdala. At the same time, the project aims to acquire technical skills in advanced molecular analysis and neuroscience methodologies, promoting integration between preclinical and translational research at the interface between metabolic and cognitive health. (AU)