Neuroprotection of Melatonin Against Lipopolysaccaride-Induced Alzeheimer's Disease in Male Albino Rats
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- Category: Vol. 82, March 2014
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Neuroprotection of Melatonin Against Lipopolysaccaride-Induced Alzeheimer's Disease in Male Albino Rats, NASHWA ELTABLAWY and OLA M. TORK
Abstract
Background: Increased levels of the amyloid ß protein (Aß), oxidative damage, mitochondrial dysfunction and pos-sibly down-regulation of cholinergic neurons are neuropatho-logical markers of Alzheimer's disease (AD). Melatonin; the neurohormone, may act as a protective agent in neurodegen-erative diseases such as Parkinson's, Alzheimer's, aging. However, the protective mechanisms of melatonin against AD as regard its relation to amyloid ß precursor protein (APP) and autophagy is still unknown.
Aim: The present study was designed to investigate the effects of early melatonin supplementation on cognitive function and biomarkers of AD including its effect on gene expression of APP and beclin1 in lipopolysaccharide (LPS)- induced Alzheimer's disease in adult male rats.
Material and Methods: The study was conducted on 24 male adult albino rats. The experimental animals were ran-domly divided into 3 groups, 8 rats each.
Group I: Control treated with vehicle, Group II (AD); lipopolysaccharide (LPS) treated (0.8mg/kg i.p. single dose), Group III: Melatonin + LPS co-treatment, melatonin (10mg/kg i.p. at 17:00hr. for 6 weeks-5 days/week) and LPS (0.8mg/kg i.p. once). Melatonin administration was started just after the single i.p. injection of LPS.
Cognitive function tests were done by T-maze during the last week of treatment.
At the end of the experimental period, all rats were sacrificed and brains were excised for the determination of the level of peroxynitrite, cardiolipin (CL) and choline acetyl transferase -activity (ChAT) and the gene expression of Amyloid ß precursor protein (APP) and Beclin-1.
Results: It was observed that melatonin treated rats showed a significant improvement of cognitive function in the form of increased percentage of alternations in T-maze, indicating improved working memory. Furthermore melatonin treatment was shown to reduce the expression of APP gene and enhance Beclin-1gene expression significantly compared with the AD rats. In addition, there was significant increase in CL and ChAT activity together with reduced peroxynitrite in melatonin treated rats.
Conclusion: Our results indicate that neuroprotection by early melatonin supplementation is partly related to reducing amyloid formation and protection of the cholinergic system. We suggest that the neuroprotective effects of melatonin are mediated by its antioxidant capacity with the improvement of mitochondrial function, increase activity of ChAT and induction of autophagy. Early rational melatonin interventions may be one of the most promising strategies in the development of approaches to prevent or retard Aß-mediated disease pro-gression.