L-carnitine attenuates Aβ₁-₄₂-induced spatial cognitive deficits and hippocampal dysfunction in a rat model of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive dysfunction and impaired synaptic plasticity. This study evaluated whether chronic L-carnitine (LC) attenuates amyloid-beta 1-42 (Aβ₁-₄₂)-induced spatial learning and memory deficits following intracerebroventricular (ICV) Aβ₁-₄₂ infusion. Forty adult male Wistar rats were randomly assigned to four groups (n = 10/group): Sham + Vehicle, Sham + LC, AD + Vehicle, and AD + LC. Following ICV Aβ₁-₄₂ infusion, LC (100 mg/kg/day, i.p.) or vehicle was administered for 28 days. Spatial learning and memory, hippocampal long-term potentiation (LTP), oxidative stress markers, Aβ plaque density, and neuronal integrity were evaluated. Compared with the AD + Vehicle-treated rats, LC attenuated Aβ₁-₄₂-induced impairments in spatial learning and memory, as indicated by reduced escape latency on training days 3-4 (both p < 0.01) and increased time spent in the target quadrant (p < 0.01). LC also improved hippocampal LTP, as reflected by a 58.4% increase in population spike (PS) amplitude potentiation (p < 0.01). Additionally, LC increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities by 40.3%, 34.4%, and 37.4%, respectively, while reducing malondialdehyde (MDA) levels by 22.0% (all p < 0.01). LC also decreased Aβ plaque density by 36.6% and increased intact pyramidal neurons by 58.3% (both p < 0.01). These findings indicate that LC mitigates Aβ₁-₄₂-induced spatial learning and memory deficits and is associated with improved hippocampal LTP, enhanced antioxidant enzyme activities, reduced lipid peroxidation and Aβ plaque density, and preserved neuronal integrity.