title: 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, TNFα and IL-1β. 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.
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Faheem
authors.initials: F
authors.lastname: Ullah
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea.
authors.forename: Tahir
authors.initials: T
authors.lastname: Ali
authors.affiliation: Department of Anatomy, Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, Khyber Pakhtunkhwa, Pakistan.
authors.forename: Najeeb
authors.initials: N
authors.lastname: Ullah
authors.affiliation: Department of Biology and Applied Life Science (BK 21), College of Natural Sciences (RINS), Gyeongsang National University, Jinju, 660-701, Republic of Korea. Electronic address: mokim@gnu.ac.kr.
authors.forename: Myeong Ok
authors.initials: MO
authors.lastname: Kim
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D003072:Cognition Disorders / Q000188:drug therapy*; D004195:Disease Models, Animal; D005690:Galactose / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D002110:Caffeine; D005690:Galactose
keywords: Caffeine; Neuroinflammation and neurodegeneration; Oxidative stress; d-galactose