Thesis Abstract

<p>               <b>ABSTRACT</b>&nbsp;</p><p>Vitamins C and E are naturally present in some foods and are available as dietary supplements. While vitamin C is also known as L-ascorbic acid, vitamin E is a generic name for tocopherols and tocotrienols each with α, β, γ and δ subunits. Neurobehavioural models have been used to study behaviour in animals with models specific for each animal species and behaviour. The aim of the study was to investigate the effect of vitamins C and E on memory and serum biochemical changes in adult mice. Twenty male and twenty female mice weighing 16-35 g were divided into 5 groups of eight mice each. The first group served as the control and received distilled water (1 ml/kg); mice in the second group served as the positive control and received soya oil (1 ml/kg), animals in group three received vitamin C (100 mg/kg), group four received vitamin E (100 mg/kg) and the last group received both vitamins C and E (100 mg/kg). The drugs were given once daily orally for a period of 21 days. Learning and memory were assessed using the elevated plus maze (EPM), object recognition and location models for memory (ORT and OLT) at the end of the experimental period. Memory index was calculated. The mice were sacrificed on day 22 and serum estrogen and testosterone levels and catalase, superoxide dismutase and glutathione peroxidase activities were also evaluated. Lipid peroxidation was determined by measuring the malondialdehyde concentration in the brain sample. The relationship between the gonadal hormone levels and the performance of animals in each of the neurobehavioural models for memory was positive. There was no significant difference in the malondialdehyde concentration (P &lt; 0.05) of all groups in the males but in females between the control and vitamin C-treated group. The activities of superoxide dismutase showed no significant difference in the males but showed significance (P &lt; 0.05) between control and treatment groups in the females, catalase showed no significant difference in the females but showed significant difference (P &lt; 0.05) between control and all groups and glutathione peroxidase showed no significant difference between all groups (P &lt; 0.05) of both males and females. The memory index for the EPM also showed significant difference (P &lt; 0.05) between the vitamin E-treated group and the soya oil and vitamin C-treated groups on the first day and between vitamin E and C-treated group on the second day in the females. In the males the significant difference was observed between control and treatment groups on both days. In the ORT model, discriminatory and recognitive index showed a significant (P &lt; 0.05) difference in the vitamin E and E+C treated groups. In the OLT model discriminatory and recognitive indices showed a significant difference (P &lt; 0.05) in the vitamin E and vitamins C+E treated groups. In conclusion, administration of vitamin C and E improved memory indices and there was a positive relationship between endogenous gonadal hormones and recognition. <br></p>

Thesis Overview

<p> <b>1.0 INTRODUCTION&nbsp;</b></p><p><b>1.1 BACKGROUND STUDY</b></p><p>Vitamin C, also known as L-ascorbic acid, is a water-soluble vitamin that is naturally present in some foods, added to others, and available as a dietary supplement and is destroyed by heat or reduced by prolonged storage (Weinstein et al., 2001). Humans, unlike most animals, are unable to synthesize vitamin C endogenously, so it is an essential dietary component (Naidu, 2003; Li, 2007). Sex steroids are hormones produced mainly by the reproductive glands, either the ovaries or testes, which share a similar basic structure of three hexane rings and a pentane ring (Gasbarri, 2010). The primary role of the gonadal steroid hormones in mammals is to regulate reproduction and related behaviours; however, both androgens and estrogens are also integrally involved in mediating higher brain function and processes, including cognition, neural development and neural plasticity (Dohanich, 2002). The hippocampal system plays an important role in memory function. Neurohormones like androgens and oestrogens are present in the hippocampus and have important roles in learning and memory (Talebi et al., 2010). Oestrogens act on the central nervous system (CNS) both through genomic mechanisms, modulating synthesis, release and metabolism of neurotransmitters, neuropeptides and neurosteroids, and through non-genomic mechanisms, influencing electrical excitability, synaptic function and morphological features. Therefore, oestrogen’s neuroactive effects are multifaceted and encompass a system that ranges from the chemical to the biochemical to the genomic mechanisms, protecting against a wide range of neurotoxic insults (Genazzani et al., 2007).<br></p><p> Vitamin C, also known as ascorbic acid AA is required for the biosynthesis of collagen, L-carnitine, and certain neurotransmitters; vitamin C is also involved in protein metabolism (Carr and Frei, 1999). Collagen is an essential component of connective tissue, which plays a vital role in wound healing. Vitamin C is also an important physiological antioxidant (Carr and Frei, 1999) and has been shown to regenerate other antioxidants within the body, including alpha-tocopherol (vitamin E) (Jacob, 2002). In addition to its biosynthetic and antioxidant functions, vitamin C plays an important role in immune function (Jacob, 2002) and improves the absorption of non-haeme iron, the form of iron present in plant-based foods. Insufficient vitamin C intake causes scurvy, which is characterized by fatigue or lassitude, widespread connective tissue weakness, and capillary fragility (Weinstein et al., 2001; Wang, 2007). Vitamin E is a generic name for tocopherols and tocotrienols. It is a family of α, β, γ and δ tocopherols and corresponding tocotrienols. Tocopherol contains saturated phytol side chains and tocotrienol have 3 double bonds in the side chain (Blatt et al., 2001; Dietrich et al., 2006). The alpha-tocopherol form of vitamin E is an important lipid-soluble antioxidant. In the brain and other tissues, alpha-tocopherol has a key role in preventing oxidant-induced lipid destruction and is, therefore, vital in maintaining the integrity of cell membranes (Blatt et al., 2001; Dietrich et al., 2006). Accordingly, vitamin E deficiency causes lipid peroxidation in brain tissues. Severe vitamin E deficiency results mainly in neurological symptoms, including impaired balance and coordination (ataxia), injury to the sensory nerves (peripheral neuropathy), muscle weakness (myopathy), and damage to the retina of the eye (pigmented retinopathy) <b>(Traber et al., 2006). </b><br></p><p><b> 1.1 Statement of Research Problem&nbsp;</b></p><p>The need to preserve cognitive functioning is present at every stage in life, whether at childhood when the focus is cognitive development or at adulthood when the need is protection or alleviation of short-term or long-term cognitive decline. This has led to promotion of the use of prescription drugs, herbal supplements, among others, in order to promote or preserve cognitive performance levels (Schmitt, 2010). Starting from adulthood, there is an age-related decline in the level of gonadal hormones, which has been correlated with impairment in some cognitive tasks (Leonard, 2011). Hence, the need for a substance that can promote cognitive development as well as protect against cognitive decline (Schmitt, 2010). Micronutrient supplementation has been shown to be associated with less cognitive decline (Morris, et al., 2002). It is reported that treatment with ascorbic acid significantly improved cognitive function in rats (Shahidi et al., 2008) and it ccould enhance learning and memory processes (Cho, et al., 2003). While a lot of work has been done on the effects of antioxidant supplementation in improving cognitive functions in aged rodents and humans (Durga, et al., 2007; Saleem, et al., 2012) there is paucity of information on effects of vitamins C and E supplementation on serum testosterone and estrogen levels as well as on learning and memory in adult mice of both sexes.&nbsp;</p><p>Thus, the question this study seeks to answer is whether vitamins C and E affect the level of the testosterone and estrogen which in turn affect learning and memory, and whether endogenous levels of these hormones can be correlated to the optimum cognitive capacity observed in adulthood.&nbsp;</p><p><b>1.2 Justification&nbsp;</b></p><p>The maintenance of brain health underpinning intact cognition is a key factor to maintaining a positive, engaged, and productive lifestyle (Stough et al., 2012). There is an age-related decline in the level of gonadal hormones, which has been correlated with impairment in some cognitive tasks such as learning and memory (Leonard, 2011). It is reported that treatment with ascorbic acid significantly improved cognitive function in aged rats (Shahidi, et al., 2008), and it can enhance learning and memory processes (Cho, et al., 2003). Vitamin E intake, from foods or supplements, was also shown to be associated with less cognitive decline with age (Morris et al., 2002). The combined effects of multiple antioxidant nutrients might be more influential on cognition than a single antioxidant as reported by Devore et al. (2010).&nbsp;</p><p><b>1.3 General Aim</b>&nbsp;</p><p>The general aim of this study was to investigate the effect of vitamins C and E on learning and memory in healthy adult mice.&nbsp;</p><p>1.3.1 Specific objectives The specific objectives of this work were as follows:&nbsp;</p><p>&nbsp; 1. To assess the effect of administration of vitamins C and E on learning and memory using the elevated plus maze for memory (EPM), object recognition test (ORT) and object location test (OLT) in mice.&nbsp;</p><p>2. To determine the effect of vitamins C and E on lipid peroxidation; malondialdehyde (MDA), and enzymatic activities; superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) in mice.&nbsp;</p><p>3. To relate the effect of endogenous testosterone and estrogen with animals performance in the EPM, ORT and OLT models for memory <br></p>