EFFECTS OF STATIN TREATMENT ON COGNITION-RELATED HIPPOCAMPAL GENE EXPRESSION IN A RAT MODEL OF CHRONIC SLEEP DEPRIVATION

Statins are widely used and safe drugs that, beyond lipid control, can affect the nervous system and exert neuroprotective effects. Given the cognitive impairment caused by chronic sleep deprivation, this study investigated how statin treatment alters hippocampal gene expression in chronically sleep-deprived rats. Male Wistar rats (CEUA 1414/2022) were divided into eight groups (N=6): control (C); sleep deprivation (D); sleep-deprived rats treated with rosuvastatin at 2.1 (R−) or 20 mg/kg/day (R+); sleep-deprived rats treated with atorvastatin at 4.2 (A−) or 20 mg/kg/day (A+); and sleep-deprived rats treated with simvastatin at 4.2 (S−) or 20 mg/kg/day (S+). Sleep deprivation was induced using an adapted multiple platform method (45 days), concomitant with drug administration. RNA sequencing was performed using the DNBSEQ-G400 platform (MGI), and differential gene expression analysis was conducted with the DESeq2 package in R. Comparisons were made relative to the D group, adopting P < 0.05. Hundreds of genes were differentially expressed; after filtering, some genes associated with cognition and inflammation exhibited notable expression patterns. In sleep-deprived rats, ADCYAP2, SOX4, PCDHGB8, DISC1, and PTGER3 were upregulated, whereas SLC7A11 was downregulated. Statin treatment attenuated these alterations, restoring a more balanced expression profile of both upregulated and downregulated genes, regardless of whether their regulation is considered beneficial or detrimental. Additionally, the neuroprotective gene NEU4 was upregulated in the A+, A−, S+, and R+ groups. These findings suggest that statins can modulate the molecular effects of chronic sleep deprivation and engage additional pathways associated with neuroprotection. FAPESP 2022/16417-7; 2025/05513-3.