Action of statins on cognitive impairment induced by sleep deprivation in rats

• Grant number: 22/16417-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2024
• 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
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Chronic sleep deprivation has become increasingly common in modern times. It is known that sleep is essential for cognitive functions such as memory consolidation and decision-making. The structures belonging to the mesocorticolimbic system are particularly affected by sleep deprivation due to their high plasticity. At the same time, neuroprotective factors also tend to have notable repercussions in these brain regions. Statins are widely used hypolipidemic drugs that are extremely pleiotropic, with diverse pharmacokinetic characteristics depending on their hydrophilic or lipophilic nature, and have shown beneficial effects on cognition. Despite this, the effect of statins on the nervous system in the face of sleep deprivation has not yet been investigated. The objective of this work is to observe the effect of rosuvastatin, atorvastatin, and simvastatin on the cognition of Wistar rats subjected to chronic sleep deprivation. Young adult male Wistar rats were divided into eight groups (N=15 per group): control group (CG) without sleep deprivation and treated with vehicle, sleep deprivation group (SDG), with a maximum of 6 hours per day and treated with the vehicle; sleep deprivation + rosuvastatin groups, receiving a single daily dose of 2.1 mg/kg (SDR-) and 20 mg/kg (SDR+) of the drug; sleep deprivation + atorvastatin groups, receiving a single daily dose of 4.2 mg/kg (SDA-) and 20 mg/kg (SDA+) of the drug; sleep deprivation + simvastatin groups, receiving a single daily dose of 4.2 mg/kg (SDS-) and 20 mg/kg (SDS+) of the drug. Treatments were carried out concomitantly starting from the 75th postnatal day, lasting for 45 days. After 23 days of treatment, the animals began a series of behavioral tests: open field, light-dark box, social recognition, radial maze, and Barnes maze for reference and working memory. Seven animals from each group were euthanized by transcardial perfusion, the brains were collected, and histological sections are being subjected to immunohistochemistry protocols for FOS, BDNF, and doublecortin (DCX). The brains of the remaining eight animals from each group were freshly collected by decapitation for quantitative analysis of the expression of 770 genes from the neuropathology panel of the Nanostring nCounter Pro platform. From the gene expression study, protein targets will be selected for quantification by western blotting. In these decapitated animals, blood was collected for serum measurement of cholesterol, triglycerides, HDL, LDL, fructosamine, glucose, CK, ALT, AST, GGT, LDH, ALP, urea, creatinine, and albumin. Interleukins (IL2, IL4, IL5, IL6, IL8, IL10, IL17), TNF-alpha, TGF-beta, and gamma interferon will also be measured to determine the inflammatory profile of the animals. For all quantitative variables, comparisons between groups will be made using statistical methods considering ± = 0.05.