Abstract
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder characterized by cognitive decline. Despite extensive research, therapeutic options remain limited. Varenicline, an α4β2 nicotinic acetylcholine receptor agonist, shows promise in enhancing cognitive function. This study aimed to evaluate varenicline's effect on memory and hippocampal activity in rat model of AD. Forty-eight adult male Wistar rats were randomly assigned to control, sham, AD, and varenicline (0.1, 1, and 3mg/kg/po for 14 days) groups. AD was induced by intracerebroventricular (i.c.v.) injection of 4µl amyloid-beta (Aβ)1-42 (1µg/µl). Spatial learning and memory, hippocampal synaptic function, and CA1 electrophysiological activity were evaluated using appropriate methods. Barnes maze and T-maze behavioral tests revealed that varenicline, particularly at 1mg/kg, significantly improved spatial memory compared to the AD group. Western blot analysis showed varenicline's ability to upregulate synaptic proteins PSD-95, synaptophysin, and GAP-43 in the hippocampus, with the most significant effects observed at 1mg/kg. Electrophysiological recordings demonstrated that varenicline at 1mg/kg enhanced hippocampal long-term potentiation (LTP), indicating improved synaptic plasticity. Single-unit recordings showed an increase in spike count with varenicline administration. These findings suggest that varenicline, particularly at 1mg/kg, ameliorates memory deficits in AD rats possibly through modulation of synaptic proteins and enhancement of hippocampal LTP and electrical activity. Further investigations are warranted to elucidate varenicline's precise mechanisms of action in alleviating AD-induced cognitive deficits and its potential as a therapeutic intervention for AD-related cognitive impairment.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call