Policosanol protects against Alzheimer's disease-associated spatial cognitive decline in male rats: possible involved mechanisms.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline and synaptic failure. The present study was designed to explore the possible protective effects of policosanol (PCO) on spatial cognitive capacity, long-term potentiation (LTP) induction, oxidant/antioxidant status, and Aβ plaques formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aβ1-40. Healthy adult male Wistar rats were randomly divided into control, sham (ICV injection of 5µl phosphate-buffered saline), AG (50mg/kg; P.O., as PCO vehicle), PCO (50mg/kg; P.O.), AD model (ICV injection of 5µl Aβ), AD + AG (50mg/kg; P.O.), and AD + PCO (50mg/kg; P.O.). Treatments were performed for eight consecutive weeks. At the end of the treatment course, spatial learning and memory functions, hippocampal long-term potentiation (LTP) induction, malondialdehyde (MDA), and total thiol group (TTG) levels, as well as the formation of Aβ plaques, were examined. The results showed that injection of Aβ reduced spatial learning and memory abilities in the Barnes maze test, which was accompanied by decreases in field excitatory postsynaptic potential (fEPSP) slope, population spike (PS) amplitude, and TTG level and increases in Aβ plaque accumulation and MDA content. In contrast, PCO treatment improved all the above-mentioned changes in the Aβ-infused rats. The results suggest that amelioration of hippocampal synaptic plasticity impairment, modulation of oxidant/antioxidant status, and inhibition of Aβ plaque formation by PCO may be the mechanisms behind its protective effect against AD-associated spatial cognitive decline.