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

RationaleAlzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by cognitive decline and synaptic failure.ObjectiveThe 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 A beta plaques formation in an AD rat model induced by intracerebroventricular (ICV) injection of A beta(1-40).MethodsHealthy adult male Wistar rats were randomly divided into control, sham (ICV injection of 5 mu l phosphate-buffered saline), AG (50 mg/kg; P.O., as PCO vehicle), PCO (50 mg/kg; P.O.), AD model (ICV injection of 5 mu l A beta), AD + AG (50 mg/kg; P.O.), and AD + PCO (50 mg/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 A beta plaques, were examined.ResultsThe results showed that injection of A beta 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 A beta plaque accumulation and MDA content. In contrast, PCO treatment improved all the above-mentioned changes in the A beta-infused rats.ConclusionsThe results suggest that amelioration of hippocampal synaptic plasticity impairment, modulation of oxidant/antioxidant status, and inhibition of A beta plaque formation by PCO may be the mechanisms behind its protective effect against AD-associated spatial cognitive decline.

Automated summary

The study aimed to investigate the potential protective effects of policosanol (PCO) on spatial cognitive capacity, long-term potentiation (LTP) induction, oxidant/antioxidant status, and Aβ plaque formation in an Alzheimer's disease (AD) rat model. The results showed that PCO treatment improved spatial learning and memory abilities, synaptic plasticity, antioxidant status, and inhibited Aβ plaque accumulation in the AD rats.