Assessment of working memory in rats subjected to chronic sleep deprivation treated with statins

• Grant number: 24/21705-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2025
• End date: January 31, 2026
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: José de Anchieta de Castro e Horta Júnior
• Grantee: Maria Luisa Dourado
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Chronic sleep deprivation has become increasingly common in contemporary society. It is known that sleep is essential for cognitive functions such as memory consolidation and decision-making. Structures within the mesocorticolimbic system are particularly compromised by sleep deprivation due to their high plasticity. At the same time, neuroprotective factors also tend to have notable effects on these brain regions. Statins are widely used hypolipidemic drugs with extensive pleiotropic effects, exhibiting diverse pharmacokinetic characteristics depending on their hydrophilic or lipophilic nature, and have demonstrated beneficial effects on cognition. Nonetheless, the impact of statins on the nervous system under sleep deprivation has yet to be investigated. The aim of this study is to observe the effect of rosuvastatin, atorvastatin and simvastatin on the working memory of Wistar rats subjected to chronic sleep deprivation. Young adult male Wistar rats were divided into eight groups (N=15 per group): control group (GC) without sleep deprivation and treated with vehicle; sleep deprivation group (GP), with a maximum of 6 hours of sleep per day and treated with vehicle; sleep deprivation + rosuvastatin groups, receiving a single daily dose of 2.1 mg/kg (GPR-) and 20 mg/kg (GPR+) of the drug; sleep deprivation + atorvastatin groups, receiving a single daily dose of 4.2 mg/kg (GPA-) and 20 mg/kg (GPA+) of the drug; sleep deprivation + simvastatin groups, receiving a single daily dose of 4.2 mg/kg (GPS-) and 20 mg/kg (GPS+) of the drug. Treatments were administered concurrently starting on postnatal day 75, lasting 45 days. After 28 days of treatment, the animals performed the working memory test in an 8-arm radial maze. Behavior was recorded, and the following parameters will be analyzed: latency to complete a visit to all arms, average visits per arm, time spent at the center of the maze, and error index. For all quantitative variables, group comparisons will be conducted using statistical methods with an alpha level of 0.05. (AU)