Neuroprotective Effects of Alpha-Tocopherol against Amyloid-β-Induced Hippocampal Synaptic Dysfunction and Oxidative Stress in a Rat Model of Alzheimer’s Disease: Behavioral, Electrophysiological, and Biochemical Insights

Alzheimer’s disease (AD) remains a major health challenge, with current treatments offering limited efficacy. Its pathologies are cognitive decline, synaptic deterioration, and heightened oxidative stress—factors that are both interconnected and amenable to targeted intervention. While antioxidant strategies have shown promise, the neuroprotective potential of vitamin E (alpha-tocopherol) against amyloid-beta (Aβ)-induced neurotoxicity requires further elucidation. The present study pioneers a comprehensive evaluation of alpha-tocopherol’s ability to mitigate cognitive deficits, synaptic impairments, and oxidative damage in an innovative rat model of AD induced by Aβ. Fifty adult male Wistar rats were assigned to control, sham, AD, vitamin E, and combined AD + vitamin E groups, with assessed through behavioral paradigms (novel object recognition, Morris water maze, and passive avoidance tests) alongside electrophysiological measures of hippocampal synaptic plasticity and, biochemical analyses, including malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant capacity (TOC), and glutathione peroxidase (GPx). The results indicated that treatment with vitamin E significantly increased the discrimination index (P<۰.۰۰۱), step-through latency (P<۰.۰۰۱), time in the target quadrant (P<۰.۰۰۱), excitatory postsynaptic potential (P<۰.۰۵) and the amplitude of population spikes (P<۰.۰۵), TAC (P<۰.۰۰۱) and GPx (P<۰.۰۰۱) relative to the AD group. It can be concluded that vitamin E decreased oxidative stress, preserved synaptic integrity, and cognitive function in Aβ-induced AD.

کلیدواژه ها:

Alpha-tocopherol ، Amyloid-β ، Cognition ، Hippocampus ، Oxidative stress ، Synaptic plasticity