Amin_2025_Neurochem.Res_50_189

This study investigates the therapeutic advantages of agomelatine in the context of Alzheimer's disease (AD) using a mouse model, with twenty healthy male SWR/J mice participating in the research. Many approaches were employed to evaluate the effectiveness of the treatments; these approaches included body weight analysis, evaluations of short-term memory, biomarker assessments, histopathological examinations, and Fourier-transform infrared (FTIR) spectroscopy. The results suggest that agomelatine treatment effectively countered the weight loss associated with AD. Importantly, agomelatine enhanced cognitive performance, as indicated by improved short-term memory in spatial recognition assessments; mice treated with agomelatine showed spontaneous alternation percentages comparable to controls, with statistically significant differences observed between AD and control groups (Dunn's post-hoc p = 0.0072). Analyses of biomarkers showed that agomelatine reduced the AD-induced elevation of acetylcholinesterase activity, interleukin-6 levels, and oxidative stress markers while increasing total antioxidant capacity. Histopathological assessments showed enhanced structural integrity in hippocampal regions. FTIR spectroscopy revealed agomelatine's protective effect on brain molecular structure, mainly through preserving lipid order in the CH stretching region and preventing protein oxidation in the C = O spectral range, both of which are typically altered by AD pathology. These results emphasize the efficacy of agomelatine and support its consideration in mitigating symptoms associated with AD etiology.