Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice.

Changes, in behaviour, oxidative markers of stress and hippocampal morphology were evaluated following aspartame administration. Mice, (20-22g each) were given vehicle (10ml/kg) or aspartame (20, 40, 80 and 160mg/kg) daily for 28days. They were tested in the Y-maze, radial-arm maze and elevated plus-maze (EPM) after the first and last dose of vehicle or aspartame; and then sacrificed. Hippocampal slices were analysed for aspartic acid, nitric oxide (NO) and superoxide dismutase (SOD); and processed for general histology and neuritic plaques. Glial fibrillary-acid protein (GFAP) expression and neuron-specific enolase (NSE) activities were determined. Radial-arm maze scores increased significantly after acute administration at 80 and 160mg/kg. Repeated administration at 20 and 40mg/kg (Y-maze) and at 40mg/kg (radial-arm maze) was also associated with increased scores, however, performance decreased at higher doses. EPM tests revealed anxiogenic responses following both acute and repeated administration. Significant increase in SOD and NO activities were observed at 40, 80 and 160mg/kg. Neuron counts reduced at higher doses of aspartame. At 40, 80 and 160mg/kg, fewer GFAP-reactive astrocytes were observed in the cornus ammonis, but increased GFAP-reactivity was observed in the dentate gyrus subgranular zone. NSE-positive neurons were readily identifiable within the dentate gyrus at the lower doses of aspartame; but at 160mg/kg, there was marked neuron loss and reduction in NSE-positive neurons. Oral aspartame significantly altered behaviour, anti-oxidant status and morphology of the hippocampus in mice; also, it may probably trigger hippocampal adult neurogenesis.

Dry-feed Added Quercetin Mitigates Cyclophosphamide-induced Oxidative Stress, Inflammation and Gonadal Fibrosis in Adult Male Rats.

BACKGROUND: Cyclophosphamide (CYP), a widely used cancer chemotherapeutic agent has been linked with male gonadotoxicity, resulting in infertility. The notion that potent antioxidants could be beneficial in mitigating CYP-induced gonadotoxicity necessitated this research. Therefore, we examined the effects of feed-added quercetin on CYP-induced gon-adotoxicity in male rats. METHODS: Male postpubertal rats were randomly assigned into six groups of 10 rats each. The normal control (fed standard rodent diet) and two groups fed quercetin-supplemented diet at 100 and 200 mg/kg of feed received normal saline intraperitoneally at 2 ml/kg daily. A fourth group which served as the CYP control (fed standard rodent diet) and the last two groups fed quercetin at 100 and 200 mg/kg of feed were administered CYP at 150 mg/kg/day. Rats were administered normal saline or CYP intraperitoneally on days 1 and 2, while standard diet or feed-added quercetin was administered daily for 21 days. On day 22, half of the animals were either sacrificed or paired with age-matched females for fertility assessment. Estimation of testosterone levels, antioxidant, anti-inflammatory markers, and histomorphological exami-nation of the testis and epididymis was also assessed. RESULTS: The administration of CYP was associated with weight loss, decreased food intake, decreased antioxidant capacity, increased gonadosomatic index, increased lipid peroxidation, sub-fertility, and histological evidence of gonadal injury. However, administration of querce-tin reversed CYP-induced changes. CONCLUSION: The result of this study suggests that dietary quercetin supplementation has the ability to mitigate CYP induced gonadotoxicity and mitigate subfertility in male rats. How-ever, further studies are required to assess its possible use in humans.

Biflavonoid quercetin protects against cyclophosphamide-induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity.

BACKGROUND: Cyclophosphamide use has been associated with increased oxidative stress in cells and tissues. Quercetin's antioxidative properties make it of potential benefit in such conditions of oxidative stress. OBJECTIVE: To assess quercetin's ability to mitigate cyclophosphamide-induced organ toxicities in rats. METHODS: Sixty rats were assigned into six groups. Groups A and D served as normal and cyclophosphamide control and were fed standard rat chow, groups B and E were fed quercetin supplemented diet (100 mg/kg of feed), while those in groups C and F were fed quercetin at 200 mg/kg of feed. Groups A-C received intraperitoneal (ip) normal saline on days 1 and 2, while D-F received ip cyclophosphamide (150 mg/kg/day on days 1 and 2). On day 21, behavioural tests were carried out, animals were sacrificed and blood samples taken. Organs were processed for histological study. RESULTS: Quercetin reversed cyclophosphamide-induced decrease in body weight, food intake and total antioxidant capacity, and increase in lipid peroxidation (p = 0.001), It also reversed derangement in levels of liver transaminase, urea, creatinine and proinflammatory cytokines (p = 0.001). Improvement in working-memory and anxiety-related behaviours were also observed. Finally, quercetin reversed alterations in levels of acetylcholine, dopamine and brain-derived neurotropic factor (p = 0.021); while reducing serotonin levels and astrocyte immunoreactivity. CONCLUSION: Quercetin shows significant ability to protect against cyclophosphamide-induced changes in rats.

Prepubertal Continuous Dietary Folate Fortification Enhances the Brain Function of Adult Mice by Modulating Antioxidant Status, Inflammation, and Brain Neurotransmitter Levels.

BACKGROUND: The benefits of folic acid supplementation have been documented in several studies. However, while evidence exists regarding its benefits for growth and haematologic parameters, its possible effects on the brain have been less examined. OBJECTIVES: The study aimed to examine the benefits of dietary folic acid supplementation (beginning in the prepubertal period) on neurobehaviour, oxidative stress, inflammatory parameters, and neurotransmitter levels in adult mice. METHODS: Forty-eight prepubertal male mice were assigned into four groups of 12 animals each. Mice were grouped into normal control (fed standard diet) and three groups fed folic acid supplemented diet at 2.5, 5, and 10 mg/kg of feed. Animals were fed a standard diet or folic acid-supplemented diet for eight weeks during which food intake and body weight were assessed. On postnatal day 78, animals were exposed to the open-field, Y-maze, radial arm maze, elevated plus maze, bar test, and models of behavioural despair. 24 hours after the last behavioural test, animals were made to fast overnight and then sacrificed by cervical dislocation. Blood was then taken for the assessment of blood glucose, leptin, and insulin levels. Homogenates of brain tissue were prepared and used for the assessment of biochemical parameters. RESULTS: Results showed a concentration-dependent increase in body weight, and improved antioxidant status, memory scores, and acetylcholine levels. Also, a decrease in food intake, blood glucose, insulin, and leptin levels was observed. A reduction in open-field behaviour, anxiety-related behaviour, and proinflammatory markers, was also observed. CONCLUSION: The beneficial effect of prepubertal continuous dietary folate fortification on the brain (as the animal ages) has been shown in this study.

Diabetes Mellitus and Energy Dysmetabolism in Alzheimer's Disease: Understanding the Relationships and Potential Therapeutic Targets.

Over the last century, there has been a gradual but sustained increase in life expectancy globally. A consequence of increased life expectancy is an associated rise in the prevalence of agerelated chronic debilitating neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease, Huntington's disease, and multiple sclerosis. These disorders, which are generally characterised by the loss of motor/sensory neurons and cognitive decline, have continued to confound researchers who are working tirelessly to define their pathogenetic mechanisms and develop effective therapies. In the last few years, there has been increasing evidence of the existence of a relationship between energy metabolism and neurodegeneration, with reports that type 2 diabetes mellitus increases the risk of AD. Evidence from preclinical and epidemiologic studies has associated dysmetabolism and dysmetabolic syndromes with the development of neurodegenerative changes. More recently, diabetes mellitus and energy dysmetabolism have been linked to the aetiopathogenesis of AD. Moreover, metabolic hormones, including ghrelin, leptin, insulin, and insulin-like growth factor (IGF)-1, have been reported to play key roles in the regulation of neuronal injury and loss in neurodegenerative diseases like AD. In this narrative review, we examine the current scientific evidence regarding the role of dysmetabolism (including diabetes mellitus and metabolic syndrome) in AD and how it impacts disease progression and the development of novel therapies in AD.

Neuroinflammation and Oxidative Stress in Alzheimer's Disease; Can Nutraceuticals and Functional Foods Come to the Rescue?

Alzheimer's disease (AD), the most prevalent form of age-related dementia, is typified by progressive memory loss and spatial awareness with personality changes. The increasing socioeconomic burden associated with AD has made it a focus of extensive research. Ample scientific evidence supports the role of neuroinflammation and oxidative stress in AD pathophysiology, and there is increasing research into the possible role of anti-inflammatory and antioxidative agents as disease modifying therapies. While, the result of numerous preclinical studies has demonstrated the benefits of anti-inflammatory agents, these benefits however have not been replicated in clinical trials, necessitating a further search for more promising anti-inflammatory agents. Current understanding highlights the role of diet in the development of neuroinflammation and oxidative stress, as well as the importance of dietary interventions and lifestyle modifications in mitigating them. The current narrative review examines scientific literature for evidence of the roles (if any) of dietary components, nutraceuticals and functional foods in the prevention or management of AD. It also examines how diet/ dietary components could modulate oxidative stress/inflammatory mediators and pathways that are crucial to the pathogenesis and/or progression of AD.

Microbiome-Based Therapies in Parkinson's Disease: Can Tuning the Microbiota Become a Viable Therapeutic Strategy?

Progressive neurodegenerative disorders such as Parkinson's disease (PD) have continued to baffle medical science, despite strides in the understanding of their pathology. The inability of currently available therapies to halt disease progression is a testament to an incomplete understanding of pathways crucial to disease initiation, progression and management. Science has continued to link the activities and equilibrium of the gut microbiome to the health and proper functioning of brain neurons. They also continue to stir interest in the potential applications of technologies that may shift the balance of the gut microbiome towards achieving a favourable outcome in PD management. There have been suggestions that an improved understanding of the roles of the gut microbiota is likely to lead to the emergence of an era where their manipulation becomes a recognized strategy for PD management. This review examines the current state of our journey in the quest to understand how the gut microbiota can influence several aspects of PD. We highlight the relationship between the gut microbiome/microbiota and PD pathogenesis, as well as preclinical and clinical evidence evaluating the effect of postbiotics, probiotics and prebiotics in PD management. This is with a view to ascertaining if we are at the threshold of discovering the application of a usable tool in our quest for disease modifying therapies in PD.

Evaluation of the Behavioural, Antioxidative and Histomorphological Effects of Folic Acid-supplemented Diet in Dexamethasone-induced Depression in Mice.

BACKGROUND: The effect of folic acid in mitigating depression has remained pivotal in research. OBJECTIVE: To determine the effects of folate supplementation on neurobehaviour oxidative stress and cerebral cortex histomorphology in the dexamethasone mouse model of depression. METHODS: Male mice were assigned to six groups (A-F) of 10 mice each. Animals in groups A and D were fed a standard diet, while those in B and E were fed folic acid supplemented diet (25 mg/kg of feed), while C and F were fed folate supplemented diet at 50 mg/kg of feed for 8 weeks. At the beginning of the sixth 6th week, mice in groups A-C were administered distilled water, while animals in groups D-F were administered dexamethasone (DEX) at 4 mg/kg body weight by gavage. Open-field, forced swim, and tail-suspension tests were conducted at the end of the experimental period, following which animals were euthanised and blood was taken for the estimation of Malondialdehyde (MDA), reduced Glutathione, Glutathione Peroxidase, Catalase activity, and Superoxide Dismutase. Sections of the cerebral cortex were prepared for histological examination. RESULTS: Folic acid supplementation increased body weight, locomotor, rearing and self-grooming behaviours, and decreased immobility time in the tail suspension and forced swim tests. There was also a reduction of lipid peroxidation and an increase in the antioxidant status. Folic acid supplementation was also found to be protective against the development of dexamethasone-induced changes in body weight, open-field behaviours, behavioural despair, oxidative stress and cerebrocortical morphology. CONCLUSION: Folic-acid supplementation improves the behavioral, some antioxidant, and cerebral morphological parameters.

Peripheral and Central Glutamate Dyshomeostasis in Neurodegenerative Disorders.

Glutamate's role as the major excitatory neurotransmitter of the mammalian central nervous system requires that its brain concentrations be kept tightly-controlled. However, in hepatic encephalopathy resulting from liver dysfunction; disruption of central neurotransmission and elevation of brain glutamate levels have been observed. These had been associated with certain neurological changes. While neurological changes resulting from hepatic encephalopathy are believed to be transient, the discovery of alterations in liver enzymes in Alzheimer's disease and the role of glutamate and glutamate homeostasis in hepatic encephalopathy have piqued interests in the possible role of glutamate, and glutamate homeostasis in neurodegenerative diseases. Here, we discuss the evidence in support of the involvement of peripheral/central glutamate homeostasis in the development of neurodegenerative disorders, as well as, the implications of such interactions in the development of new therapies for neurodegenerative disorders.

Concentration-dependent Effects of Dietary L-Ascorbic Acid Fortification in the Brains of Healthy Mice.

BACKGROUND: Ascorbic acid (AA) is a water-soluble vitamin that is concentrated in the brain in large quantities. There have been reports that it is essential for proper brain functioning. However, there is insufficient information on the possible effects of dietary fortification with AA on the health of the brain. OBJECTIVE: This study examined the effects of dietary fortification of rodent chow with AA on neurobehaviour, antioxidant status, lipid peroxidation, and inflammatory/apoptotic markers in the brain of healthy mice. METHODS: Mice were randomly assigned into four groups of ten animals each. Groups were normal control [fed rodent chow], and three groups were fed AA-fortified chow at 100, 200, and 300 mg/kg of feed, respectively, for eight weeks. Behavioural tests {Open field, Y-maze, radial-arm maze, and elevated plus maze (EPM)} were carried out on day 57. Twenty-four hours after the last behavioural test, animals were euthanised, and the brains were excised and homogenised for assessment of brain acetylcholinesterase activity, lipid peroxidation, antioxidant status, inflammatory and apoptotic markers. RESULTS: Ascorbic acid fortified diet was associated with concentration-dependent changes in body weight, open-field behaviours, working-memory, and anxiety indices. Also, brain levels of malondialdehyde, caspase-3, and TNF-α decreased, while superoxide dismutase activity, total antioxidant capacity, and IL-10 level increased. CONCLUSION: Dietary AA fortification with concentrations up to 300 mg/kg of feed was associated with sustained improvement in neurobehavioural and biochemical parameters in the brain of healthy mice, reiterating additional health benefits of AA fortification beyond the prevention of nutritional deficiencies.

Parkinson's Disease: Is there a Role for Dietary and Herbal Supplements?

Parkinson's Disease (PD) is characterised by degeneration of the neurons of the nigrostriatal dopaminergic pathway of the brain. The pharmacological cornerstone of PD management is mainly the use of dopamine precursors, dopamine receptor agonists, and agents that inhibit the biochemical degradation of dopamine. While these drugs initially provide relief to the symptoms and improve the quality of life of the patients, progression of the underlying pathological processes, such as oxidative stress and neuroinflammation (which have been strongly associated with PD and other neurodegenerative disorders), eventually reduce their benefits, making further benefits achievable, only at high doses due to which the magnitude and frequency of side-effects are amplified. Also, while it is becoming obvious that mainstream pharmacological agents may not always provide the much-needed answer, the question remains what succour can nature provide through dietary supplements, nutraceuticals and herbal remedies? This narrative review examines current literature for evidence of the possible roles (if any) of nutraceuticals, dietary supplements and herbal remedies in the prevention or management of PD by examining how these compounds could modulate key factors and pathways that are crucial to the pathogenesis and/or progression of PD. The likely limitations of this approach and its possible future roles in PD prevention and management are also considered.

Lepidium meyenii Supplemented Diet Modulates Neurobehavioral and Biochemical Parameters in Mice Fed High-Fat High-Sugar Diet.

BACKGROUND: Metabolic syndrome has been associated with an increased risk of cardiovascular disease, diabetes mellitus, and neurodegenerative disorders. Known side-effects of currently- available drugs necessitate the search for possibly better treatment options. OBJECTIVE: This study examined the effects of dietary lepidium meyenii (MACA) supplementation on neurobehaviour, metabolic profile, levels of inflammatory markers, and oxidative stress parameters in a mouse model of metabolic syndrome. METHODS: Mice were randomly assigned into 8 groups of ten animals each. Groups consist of standard diet (SD) control, high fat/high sugar (HFHS) control and three groups each of lepidium meyenii incorporated into either SD or HFHS diet at 0.1, 0.2 and 0.4%. Mice were fed for seven weeks, and body weight was measured weekly. Open-field behaviors and radial-arm/Y-maze spatial memory were scored at the end of the study. Twenty-four hours after the last behavioral test, fasting blood glucose levels were estimated. Animals were then euthanized, and blood was drawn for estimation of serum lipid profile. Whole brains were excised, weighed and homogenized to estimate the levels of lipid peroxidation, inflammatory markers, antioxidant status, and acetylcholinesterase activity. RESULTS: MACA-supplemented diet was associated with a decrease in body weight gain, an increase in food intake (at lower concentrations), suppression of grooming behavior, and decrease in acetylcholinesterase activity. MACA-supplement also reversed HFHS-induced memory impairment, anxiety, hyperglycaemia, lipid derangement, oxidative stress, and derangement of inflammatory markers. CONCLUSION: Dietary supplementation with MACA shows beneficial effects in mitigating the effects of metabolic syndrome on the brain in mice.

Anti-Inflammatory, Anti-Oxidant, and Anti-Lipaemic Effects of Daily Dietary Coenzyme-Q10 Supplement in a Mouse Model of Metabolic Syndrome.

BACKGROUND: The dietary model of metabolic syndrome has continued to aid our understanding of its pathogenesis and possible management interventions. However, despite progress in research, therapy continues to be challenging for humans; hence, the search for newer treatment and prevention options continues. OBJECTIVE: The objective of this study was to evaluate the impact of dietary CQ10 supplementation on metabolic, oxidative, and inflammatory markers in a diet-induced mouse model of metabolic syndrome. METHODS: Mouse groups were fed a Standard Diet (SD), High-Fat High-Sugar (HFHS) diet, and SD or HFHS diet (with incorporated CQ10) at 60 and 120 mg/kg of feed. At the completion of the study (8 weeks), blood glucose levels, Superoxide Dismutase (SOD) activity, plasma insulin, leptin, adiponectin, TNF-α, IL-10, serum lipid profile, and Lipid Peroxidation (LPO) levels were assessed. The liver was either homogenised for the assessment of antioxidant status or processed for general histology. RESULTS: Dietary CQ10 mitigated HFHS diet-induced weight gain, decreased glucose, insulin, and leptin levels, and increased adiponectin levels in mice. Coenzyme-Q10 improved the antioxidant status of the liver and blood in HFHS diet-fed mice while also decreasing lipid peroxidation. Lipid profile improved, level of TNF-α decreased, and IL-10 increased following CQ10 diet. A mitigation of HFHS diet-induced alteration in liver morphology was also observed with CQ10. CONCLUSION: Dietary CQ10 supplementation mitigates HFHS diet-induced changes in mice, possibly through its anti-oxidant, anti-lipaemic, and anti-inflammatory potential.

An Investigation of the Anti-Parkinsonism Potential of Co-enzyme Q10 and Co-enzyme Q10 /Levodopa-carbidopa Combination in Mice.

BACKGROUND: Despite decades of research, neurodegenerative disorders like Parkinson's disease remain a leading cause of disability worldwide, due to the insufficient reduction of disease burden by available medications. Recently, the benefits of dietary supplements like co-enzyme Q10 in neurodegenerative diseases have been reported. ; Aim: The protective effects of supplemental co-enzyme Q10 (CQ10) and possible additive benefits of CQ 10/Levodopa-Carbidopa (LD) in Chlorpromazine (CPZ)-induced Parkinsonism-like changes in mice were investigated. ; Methods: Male mice were assigned to ten groups of 30 mice each. Groups included: Vehicle control (fed Standard Diet (SD), and given intraperitoneal {ip} plus oral saline), LD group (fed SD, and given ip saline plus oral LD), two groups fed CQ10-supplemented diet (at 60 and 120 mg/kg of feed), and given ip plus oral saline, CPZ group (fed SD, and given ip CPZ plus oral saline), CPZ/LD group (fed SD, and given ip CPZ plus oral LD), two groups fed CQ10-supplemented diet (at 60 and 120 mg/kg of feed) and given ip CPZ plus oral saline, and another two groups fed CQ10-supplemented diet (at 60 and 120 mg/kg of feed) and given ip CPZ plus oral LD. The total duration of study was 21 days, and treatments were administered daily. Bodyweight and food intake were measured weekly, while neurobehavioural and biochemical tests were assessed at the end of the experimental period. ; Results: CQ10-supplementation was protective against CPZ-induced parkinsonism-like changes including, reduction in mortality, the reversal of retardation of open-field behaviours and reduction of catalepsy, increase in dopamine levels and decreased oxidative stress. CQ10 also showed significant improvements in these parameters when co-administered with LD. CQ10 (in groups administered CPZ/CQ10 60) showed greater benefit over LD on anxiety-related behaviours and also had additive benefits on working-memory. ; Conclusion: Dietary CQ10-supplementation was associated with demonstrable benefits in CPZinduced Parkinsonism-like changes in mice.

Multidrug-Resistance Genes in Pseudomonas aeruginosa from Wound Infections in a Tertiary Health Institution in Osogbo, Nigeria.

BACKGROUND: Multidrug Resistant Pseudomonas aeruginosa (MDRPA) is a ubiquitous opportunistic organism that poses threat to the management of infections globally. OBJECTIVES: The objectives of the current research were to assess the antibiotic resistance profiles as well as Multiple Antibiotic Resistance (MAR) Index of clinical isolates of P. aeruginosa associated with wound infections. Presence of Extended Spectrum Beta Lactamase genes (bla CTX-M, bla SHV and bla TEM) and Carbapenemase genes (bla KPC and blaNDM) were also determined among the isolates. METHODS: Swab samples were collected from 255 patients with wound infections. Bacterial identification was done by standard diagnostic tests. The identity of isolates was confirmed by the detection of the exoA gene using the PCR technique. Antibiotic susceptibility testing and resistance profile were determined using the disc diffusion method. Resistance genes were amplified by the PCR method. RESULTS: A total of 235 (92.2%) bacterial isolates were recovered from the wounds of the 255 patients, of these, 124 (52.8%) were Gram-negative bacilli while the remaining 111 (47.2%) were Gram-positive cocci. A total of 69 Pseudomonas aeruginosa strains were recovered from the wound specimens. Imipenem was the most effective antibiotic against these isolates (92.8% isolates were susceptible) while all isolates were resistant to Meropenem, Cefepime, Ticarcillin, Amoxicillin-clavulanic acid, Cefotaxime, Ampicillin and Cefpodoxime. All 69 Pseudomonas aeruginosa isolates were multidrug resistant (MDR). Of the isolates selected for PCR, all were positive for TEM, CTX-M and SHV genes while one-third were blaKPC and blaNDM producers. CONCLUSION: This study demonstrated high prevalence of carbapenem-resistant strains of P. aeruginosa, suggesting that there is an urgent need in Nigeria for the enactment and enforcement of policies and necessary laws restricting the availability and indiscriminate use of antibiotics.

African Plants with Antidiabetic Potentials: Beyond Glycaemic Control to Central Nervous System Benefits.

BACKGROUND: For centuries, humans have used medicinal plants in the management of both acute and chronic diseases. Currently, the practice of using medicinal plants to manage diseases is becoming increasingly-common; especially in medium to low-income economies where the cost of, or ease of access to orthodox medications are limitations to their effective and sustained use. Diabetes mellitus is a chronic disease whose prevalence continues to increase worldwide. An aspect of diabetes mellitus that causes significant morbidity is its neurological complications, which are known to be associated with an enormous economic burden and reduction in quality of life. OBJECTIVES: While research continues to demonstrate that a wide range of plants that are indigenous to Africa have significant antihyperglycaemic properties, scientific information on the neurobehavioural and/or neuromorphological effects of these plants appear to be lacking. Also, their possible benefits in the prevention or amelioration of the neurological complications of diabetes mellitus remain generally unexamined. METHODOLOGY: In this narrative review, we the examine available scientific literature dealing with the neurobehavioural and/or neuromorphological profiles of selected African plants with substantiated antihyperglycaemic properties; aiming to highlight their potential applications in the prevention and management of the neurological complications of diabetes mellitus. RESULTS: This review demonstrates that a number of the African plants with antidiabetic properties also exhibit central nervous system effects. CONCLUSION: While the neurobehavioural and neuromorphological effects of some of these plants had been investigated in animal models of DM; their possible roles in the prevention or amelioration of the neurological complications of DM are yet to be established.

Dietary glutamate and the brain: In the footprints of a Jekyll and Hyde molecule.

Glutamate is a crucial neurotransmitter of the mammalian central nervous system, a molecular component of our diet, and a popular food-additive. However, for decades, concerns have been raised about the issue of glutamate's safety as a food additive; especially, with regards to its ability (or otherwise) to cross the blood-brain barrier, cause excitotoxicity, or lead to neuron death. Results of animal studies following glutamate administration via different routes suggest that an array of effects can be observed. While some of the changes appear deleterious, some are not fully-understood, and the impact of others might even be beneficial. These observations suggest that with regards to the mammalian brain, exogenous glutamate might exert a double-sided effect, and in essence be a two-faced molecule whose effects may be dependent on several factors. This review draws from the research experiences of the authors and other researchers regarding the effects of exogenous glutamate on the brain of rodents. We also highlight the possible implications of such effects on the brain, in health and disease. Finally, we deduce that beyond the culinary effects of exogenous glutamate, there is the possibility of a beneficial role in the understanding and management of brain disorders.

An Assessment of the Effects of Azodicarbonamide-containing Diet on Neurobehaviour, Brain Antioxidant Status and Membrane Lipid Peroxidation Status in Rats.

BACKGROUND: Azodicarbonamide is a dough-enhancer used in the process of breadmaking in countries like Nigeria. While there have been suggestions that it is a sensitizer of the respiratory system, there is a dearth of information on its effects on the central nervous system. AIM: This study assessed the effects of azodicarbonamide on the central nervous system (ADA) in rats. OBJECTIVE: The effects of ADA-containing diet on neurobehaviour, brain antioxidant status, and neuromorphology of selected brain regions in rats were examined. METHODS: Forty adult rats were randomly-assigned into four groups of ten rats each, and were given standard diet or diet containing ADA at 1, 2 and 4% respectively. Rats were fed a standard diet or ADA-containing diet for a period of 28 days. Weekly body weight assessment and daily estimation of food intake were done. Behavioural tests {in the Open field, Y-maze, radial-arm maze, and Elevated Plus Maze (EPM)} were conducted on day 29. Twenty-four hours after the last behavioural test, animals were euthanised, whole brains were dissected, weighed, and either homogenised for assessment of lipid peroxidation and antioxidant status; or sectioned and processed for general histology. RESULTS: Consumption of ADA-containing diet was associated with a significant decrease in weight gain/food intake, and significant suppression of horizontal locomotion and rearing behaviours; however, grooming activity increased significantly. Also, there was a significant reduction of open-arm time in the EPM and a significant increase in Y-maze alternation (at the lowest concentration of ADA). ADA-containing diet was not associated with significant changes in brain oxidative status or neuromorphology. CONCLUSION: The study showed that while ADA-containing diet may alter neurobehaviour in rats; this was not associated with evidence of brain oxidative stress or neuro-histomorphological alterations.

High Dietary Fat Modulates Neurobehavioural Effect of Lopinavir/ Ritonavir in Mice.

BACKGROUND: Lopinavir/Ritonavir (LR) is a protease inhibitor used human immunodeficiency virus infection management. There have been issues regarding the effects of fat on LR efficacy and the possibility of neurological deficits following prolonged use, there is however a dearth of research examining this. AIMS: The effects of LR administered with normal or High-Fat Diet (HFD) on neurobehaviour, neurochemistry and oxidative stress in healthy mice were examined. METHODS: Mice were randomly-assigned into eight groups of ten (n=10) animals each. The groups were normal control [Standard Diet, (SD)], HFD control, 3 groups of LR incorporated into SD (100/25, 200/50 and 400/100 mg/kg of feed), and 3 groups of LR with HFD (100/25, 200/50 and 400/100 mg/kg of feed). Mice were fed daily for six weeks, following which open field, elevated-plus maze (EPM), radial-arm maze and Y-maze behaviours were scored. Twenty-four hours after tests, mice were euthanised and brains were homogenised for estimation of oxidative stress, L-glutamate level and acetylcholinesterase activity. RESULTS: LR was associated with a reduction in HFD-induced weight gain, suppression of open-field behaviours with SD, and counteraction of HFD-induced changes in working-memory, open-field and anxiety-related behaviours. Also, LR causes increased lipid peroxidation and superoxide dismutase activity; and a decrease in brain glutamate, irrespective of dietary composition. Increased fat catabolism leading to increased oxidative stress could possibly account for the weight changes, while a decrease in brain glutamate could account for the changes in open-field behaviours in mice fed SD. CONCLUSION: LR alters neurobehaviour, oxidative stress and brain glutamate in mice; however, only its effects on neurobehaviour are affected by diet.

Food-added azodicarbonamide alters haematogical parameters, antioxidant status and biochemical/histomorphological indices of liver and kidney injury in rats.

OBJECTIVES: Azodicarbonamide (ADA) is a dough enhancer currently used as a replacement for potassium bromate in the process of bread-making in countries such as Nigeria. However, comprehensive information on the toxicological profile of ADA is not readily available. The present study investigated the toxicological effects of ADA in rats. METHODS: Twenty-four adult rats were randomly assigned into four groups of six rats each. Animals in group A served as the control (administered standard diet), whereas animals in groups B, C and D were fed ADA in food at 1, 2 and 4%, respectively. Standard or ADA diet was fed to the animals daily for a period of 28 days. Body weight was measured weekly, whereas food and water consumption was measured daily. On day 28, animals were fasted overnight after which they were euthanised. Blood samples taken were used for assessment of fasting blood glucose, haematological parameters, serum lipids, antioxidant status, lipid peroxidation status, electrolytes and urea, plasma proteins and biochemical parameters of liver and kidney injury. The liver and kidneys were then excised and processed for general histological study. RESULTS: The results showed that repeated administration of ADA was associated with dose-related decrease in weight gain, decrease in overall food consumption, decreased superoxide dismutase activity/glutathione level and increased lipid peroxidation. There was also biochemical and morphological evidence of liver and kidney injury. CONCLUSIONS: These findings suggest that food-added ADA could be injurious to the body cells and organs in rats.