Caffeine prevents D-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain

Abstract

D-galactose has been considered a senescent model for age-related neurodegenerative disease. It induces oxidative stress which triggers memory impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant and has been used in various model of neurodegenerative disease. Nevertheless, the effect of caffeine against D-galactose aging murine model of age-related neurodegenerative disease elucidated. Here, we investigated the neuroprotective effect of caffeine against D-galactose. We observed that chronic treatment of caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory impairment and synaptic markers (Synaptophysin and PSD95) in the D-galactose treated rats. Chronic caffeine treatment reduced the oxidative stress via the reduction of 8-oxoguanine through immunofluorescence in the D-galactose-treated rats. Consequently caffeine treatment suppressed stress kinases p-JNK Additionally, caffeine treatment significantly reduced the D-galactose-induced neuroinflammation through alleviation of COX-2, NOS-2, TNF alpha and IL-1 beta. Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio, caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the immunohistochemical results of Nissl and Fluro-Jade B staining showed that caffeine prevented the neurodegeneration in the D-galactose-treated rats. Our results showed that caffeine prevents the D-galactose-induced oxidative stress and consequently alleviated neuroinflammation and neurodegeneration; and synaptic dysfunction and memory impairment. Therefore, we could suggest that caffeine might be a dietary anti-oxidant agent and a good candidate for the age-related neurodegenerative disorders. (C) 2015 Elsevier Ltd. All rights reserved.