Acetyl-l-carnitine rescues scopolamine-induced memory deficits by restoring insulin-like growth factor II via decreasing p53 oxidation

• ALC supplement reverses learning/memory defects induced by scopolamine.
• ALC reverses LTP impairment, dendritic abnormalities, and synaptic proteins loss.
• ALC decreases oxidative products and increases the activity of SOD.
• ALC recovers the suppressed activity of p53 caused by oxidative stimuli.
• ALC restores levels of insulin-like growth factor II.

Alzheimer's disease (AD) is characterized by the cholinergic neurons loss and impairments of learning and memory. Scopolamine is common used to imitate AD pathological features and also causes an obvious oxidative stress. In this study, we found that intraperitoneal administration of supplementary acetyl-l-carnitine partially reverses the learning and memory defects induced by scopolamine. We also found that acetyl-l-carnitine reverses the impairment of long-term potentiation, dendritic abnormalities, and the impaired recruitment of synaptic protein. The beneficial effects of acetyl-l-carnitine may occur through amelioration of oxidative stress because it effectively decreases the levels of oxidative products and increases the activity of superoxide dismutase; this leads to a recovery in the suppressed activity of p53 caused oxidative stimuli, which in turn restores levels of insulin-like growth factor II, an important hormone for learning and memory. Our study provides the first evidence of the potential utility of acetyl-l-carnitine in treating the synaptic disorders prevalent in AD and other neurodegenerative diseases.This article is part of the Special Issue entitled ‘The Synaptic Basis of Neurodegenerative Disorders’.