title: Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer's disease.
abstract: Exploring the links between neural pathobiology and behavioural deficits in Alzheimer's disease (AD), and investigating substances with known therapeutic advantages over subcellular mechanisms underlying these dysfunctions could advance the development of potent therapeutic molecules for AD treatment. Here we investigated the efficacy of ascorbic acid (AA) in reversing aluminium chloride (AlCl3)-induced behavioural deficits and neurotoxic cascades within prefrontal cortex (PFC) and hippocampus of rats. A group of rats administered oral AlCl3(100mg/kg) daily for 15days showed degenerative changes characterised by significant weight loss, reduced exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety during behavioural assessments compared to control. Subsequent analysis showed that oxidative impairment-indicated by depleted superoxide dismutase and lipid peroxidation (related to glutathione-S-transferase activity), cholinergic deficits seen by increased neural acetylcholinesterase (AChE) expression and elevated lactate dehydrogenase underlie behavioural alterations. Furthermore, evidences of proteolysis were seen by reduced Nissl profiles in neuronal axons and dendrites which correspond to apoptotic changes observed in H&E staining of PFC and hippocampal sections. Interestingly, AA (100mg/kg daily for 15days) significantly attenuated behavioural deficits in rats through inhibition of molecular and cellular stressor proteins activated by AlCl3.Our results showed that the primary mechanisms underlying AA therapeutic advantages relates closely with its abilities to scavenge free radicals, prevent membrane lipid peroxidation, modulate neuronal bioenergetics, act as AChE inhibitor and through its anti-proteolytic properties. These findings suggest that supplementing endogenous AA capacity through its pharmacological intake may inhibit progression of AD-related neurodegenerative processes and behavioural alterations.
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria. Electronic address: olajide.oj@unilorin.edu.ng.
authors.forename: Olayemi Joseph
authors.initials: OJ
authors.lastname: Olajide
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Emmanuel Olusola
authors.initials: EO
authors.lastname: Yawson
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Ismail Temitayo
authors.initials: IT
authors.lastname: Gbadamosi
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Tolulope Timothy
authors.initials: TT
authors.lastname: Arogundade
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Ezra
authors.initials: E
authors.lastname: Lambe
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Kosisochukwu
authors.initials: K
authors.lastname: Obasi
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Ismail Tayo
authors.initials: IT
authors.lastname: Lawal
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Abdulmumin
authors.initials: A
authors.lastname: Ibrahim
authors.affiliation: Division of Neurobiology, Department of Anatomy, Faculty of Basic Medical Sciences, College of Health Sciences, University of Ilorin, Nigeria.
authors.forename: Kehinde Yomi
authors.initials: KY
authors.lastname: Ogunrinola
mesh_terms: D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D002712:Chlorides / Q000633:toxicity*; D004195:Disease Models, Animal; D018450:Disease Progression; D005106:Exploratory Behavior / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D015227:Lipid Peroxidation; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats
chemical_list: D017607:Aluminum Compounds; D002712:Chlorides; D000077410:Aluminum Chloride; D001205:Ascorbic Acid
keywords: Cholinergic transmission; Neurodegeneration; Neuronal bioenergetics; Oxidative redox; Proteolysis