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The hippocampus is involved in learning and memory processes, an integral component of cognitive function. The aim of this study is to assess the efficacy of quercetin on manganese-induced neurotoxicity in the hippocampus of the adult mice. In this study, 40 adult mice of average weight of 18 –29g were randomly distributed into five groups of eight each. The brain was harvested and the region of the hippocampus was grossed for histological and immunohistochemical analysis. The results revealed a significant increased level of oxidative stress markers of manganese treated mice when compared with the normal control and quercetin treated animals (p<0.05). Immunohistochemical analysis also showed a decrease expression of Tumour necrosis factor alpha (TNFα) with quercetin treated animals when compared with manganese treated animals indicating its neuroprotective function. In addition, quercetin treated animals all had an improved working spatial memory in Y-maze test. The histological results also revealed a degeneration of pyramidal cells with a characteristic pyknotic activities at the granular layer of the hippocampus leading to neuronal integrity damage following chronic exposure to manganese but normal architectural design was however maintained with quercetin. Conclusively, exposure to manganese in excess may have adverse effect on extensive neuronal degeneration that could affect the learning, memory and possibly spatial navigation ability of mice and quercetin attenuates this induced neurotoxicity via inhibition of oxidative stress and reduction of TNF expression. DOI: 10.14302/issn.2577-2279.ijha-20-3634 INTERNATIONAL JOURNAL OF HUMAN ANATOMY ISSN NO: 2577-2279 Freely Available Online www.openaccesspub.org | IJHA CC-license DOI : 10.14302/issn.2577-2279.ijha-20-3634 Vol-2 Issue 3 Pg. no.24 Introduction Neurotoxicity refers to a kind of toxicity by which different agents such as biological, chemical, or physical could cause an adverse effect on the anatomy of the central and peripheral neurons [1]. It could be as a result of exposure to a substance known as neurotoxin to alter the normal structure of the nervous system and this might result into damage to nervous tissue which could perhaps destroy neurons [1]. Exposure to other heavy metals and chemicals such as pesticides in the environment may lead to neurotoxicity [2]. Neurodegeneration is the continuous process of losing the structure or function of neurons which can lead to death of neurons and these have a way to affect person’s movement and cognitive function [3]. Neurodegenerative diseases are complex type of diseases that involves neurodegeneration in different areas of the brain. These diseases are characterized by a progressive degeneration of the both structure and function of the central nervous system. Most therapy adopted for neurodegenerative diseases such as Parkinson’s diseases and Alzheimer’s disease have been reported not to be completely efficient in the management of the disorders thereby leading into a state of progressive degeneration and death of neurons. Manganese is an essential trace element present naturally in foods such soybeans, leafy vegetables, coffee and available as a dietary supplement and also a cofactor for many enzymes [4, 5]. Evidence have shown that 1-100mcg/L of water contains small amounts of manganese [6]. Evidence has not shown that high dietary manganese intakes could cause manganese toxicity [7]. However, manganese toxicity has been reported in an individual working as welders and miners or those exposed to high amounts of manganese as result of chronic inhalation of manganese dust [8]. Manganese toxicity is known to affects the central nervous system resulting into impaired fine motor and cognitive functions especially those related to memory and learning [8]. However, the neural mechanism of alteration in hippocampus by manganese to affect cognition is still unclear, hence the reason for the study to understand the efficacy of quercetin on manganese-induced neurotoxicity. Quercetin is grouped as one of the six subclasses of flavonoid compounds found in fruits and vegetables [9]. Evidences revealed that quercetin have a therapeutic potential for the prevention of different diseases such as cardiovascular disease and neurodegenerative diseases [9, 10]. However, quercetin has been shown to affect its antioxidant and antiinflammatory properties in several areas of animal models as well as in humans by upregulating the signalling pathways via inhibition of oxidative stress markers and apoptotic factor expression involved [9, 10]. For this present study, quercetin has been used on animal model to investigate its antioxidant activities on the cell death induced by excessive consumption of the manganese. Materials and Methods Experimental Animals 40 adult male BALB/c mice weighing 18-29g were purchased from Tolex Animal holding, Ekiti State, Nigeria. Approval was sought and obtained from the ABUAD Ethical committee on animal use. The animals were housed in well-ventilated cages and maintained under standard laboratory condition of temperature, humidity and light. The animals were allowed to acclimatize for two weeks and fed with rodent meal (ADEHEZ Rodent Feed, Ilorin, Nigeria) and drinking water was made available ad libitum. After the acclimatization period, they were reweighed and Corresponding author: Adeshina Oloruntoba Adekeye, Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria, Email: cyberdex21@gmail.com

Quercetin Attenuates Manganese-Induced Neurotoxicity in Mice Hippocampus by Regulation of Oxidative Stress and Tumour Necrosis factor Alpha Expression