Atorvastatin ameliorates cerebral cortical pathological and cognitive alterations in aged rats: Histological &...

Aging is an important risk factor for neurodegenerative disease and requires the development of safe and widely accessible strategies to mitigate brain aging. Atorvastatin, primarily recognized for its cholesterol-lowering properties, has largely unexplored potential in modulating autophagy and safeguarding against age-related cognitive decline. The current study aimed to explore the potential beneficial impact of atorvastatin on structural and functional brain alterations in aged rats by analyzing its influence on autophagy and related processes, including apoptosis, inflammation, and oxidative stress. The study involved twenty-four rats, which were separated into three distinct groups: the adult control group (3-4 months old), the untreated aged group (20-24 months old) that received saline orally, and the aged treated group (20-24 months old) that received atorvastatin orally for 30 days at a dose of 20 mg/kg. Memory performance was evaluated using behavioural assessments. The cortical levels of oxidative stress markers, namely Nrf-2, MDA, GSH, and SOD, along with inflammatory mediators such as TNF-α and IL-1β, were quantified. Histopathological changes and immune staining of NF-κB, Nrf-2, TNF-α, Anti-SQSTM1/p62, LC3, and CD68 were evaluated. Furthermore, the levels of p62, caspase-3, and SIRT1 expression were determined. Atorvastatin enhanced memory function in aged rats. This was achieved by restoring the oxidative-antioxidant balance in the cortex, as evidenced by increased levels of Nrf-2, GSH, and SOD, along with a reduction in MDA levels. TNF-α, IL-6, and NF-κB cortical expression was suppressed, indicating their anti-inflammatory effects. Furthermore, autophagy was enhanced, as shown by elevated LC3 and decreased p62 expression, whereas apoptosis was mitigated through the downregulation of Caspase-3. Histological analysis corroborated the preservation of cortical structure and protection against neurodegenerative changes associated with aging. In conclusion, atorvastatin showed neuroprotective impact in this aged rat model by reducing oxidative stress, inflammation, and apoptosis, while modulating autophagy markers. These preclinical findings warrant further investigation, including clinical studies, to evaluate their therapeutic potential in humans.