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.

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.

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.

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.

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.

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.

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.

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.

Dietary zinc supplement militates against ketamine-induced behaviours by age-dependent modulation of oxidative stress and acetylcholinesterase activity in mice.

BACKGROUND: The potential differential modulatory effects of zinc-supplemented diet on ketamine-induced changes in behaviours, brain oxidative stress, acetylcholinesterase activity, and zinc (ZN) levels were examined in prepubertal and aged mice. METHODS: Aged and prepubertal mice were divided into 2 groups consisting of 80 aged and 80 prepubertal mice, each having 8 treatment groups of 10 animals each. The treatment groups are: vehicle control group (fed standard diet and given intraperitoneal {ip} normal saline), three groups fed ZN-supplemented diet (at 25, 50 and 100 mg/kg of feed) and given ip normal saline, ketamine control group (fed standard diet and given ip ketamine), and finally another three groups fed ZN-supplemented diet (at 25, 50 and 100 mg/kg of feed) and given ip ketamine. Intraperitoneal normal saline (at 2 ml/kg/day) or ketamine (at 30 mg/kg/day) were administered during the last 10 days of study. On day 60, animals were exposed to the open-field, Y-maze, radial-arm maze, and elevated plus maze following which they were euthanised; blood and brain homogenate were used for assessment of biochemical parameters. RESULTS: Zinc supplementation was associated with an increase in food intake and body weight (in both age groups), a reduction in ketamine-induced increase in locomotion, rearing and grooming, and significantly higher working-memory scores (compared to ketamine control). Also, there was a decrease in anxiety-related behaviours, enhanced antioxidant status, reduced lipid peroxidation, and reduced acetylcholinesterase activity. CONCLUSION: In conclusion, dietary ZN supplementation was associated with variable degrees of prevention of ketamine-induced changes, depending on the age of animals.

Prevalence of Multi-Drug Resistant Tuberculosis among Tuberculosis Patients Attending Chest Clinics in Osun-State, Nigeria.

BACKGROUND: The development of multidrug-resistant tuberculosis (MDR-TB) poses a considerable threat to tuberculosis control programmes in Nigeria. There is an increase in the prevalence of MDR-TB worldwide both among new tuberculosis cases as well as previously-treated ones. There is also a rise in transmission of resistant strains due to an increase in MDR-TB patients largely due to the poor drug compliance and the impact of Human immunodeficiency virus infection. Therefore, we intend to determine the extent of MDR-TB among attendees of chest clinics in Osun-State, Nigeria. OBJECTIVES: The objective of this study was to determine the prevalence of MDR-TB among confirmed tuberculosis patients attending chest clinics in Osun-State, Nigeria. METHODS: This study was conducted among 207 attendees of chest clinics in Osun-State between June, 2015 and October 15, 2016. Sputum and blood samples of the participants were collected. GeneXpert test was carried out first on the samples for simultaneous identification of MTB and rifampicin resistance. Sputum samples were cultured on Lowenstein-Jensen (L-J) medium using N-acetyl-Lcysteine- sodium hydroxide (NALC-NaOH) decontamination method. Drug susceptibility testing (DST) to three first-line drugs was carried out using the proportion DST method. RESULTS: The prevalence of MTB was found to be 27.5% while the prevalence of MDR-TB from the fifty-seven isolates was 10.5%. Previously treated and new cases had a prevalence of 7.0% and 3.5% MDR-TB, respectively. Seventy (33.8%) participants were positive for HIV infection, out of which twenty-six (12.6%) had co-infection of tuberculosis and HIV. The mono-resistance rates of the three first-line drugs used were: 5.3% and 8.7% for ethambutol (EMB) and isoniazid (INH), respectively. No isolate had mono-resistance (0%) to rifampicin (RIF). CONCLUSION: This study observed the prevalence of 27.5% MTB and a prevalence of 10.5% MDR-TB among the MTB isolates. The prevalence of TB is high in Osun State. MDR-TB prevalence is higher compared with the national estimate of MDR-TB (5.1%) of 2017. Resistant TB is a threat to national tuberculosis control and it is recommended that all the facilities be equipped to cater to its diagnosis.

An Evaluation of the Effects of Pyridoxal Phosphate in Chlorpromazineinduced Parkinsonism using Mice.

BACKGROUND: Parkinsonism is a neurodegenerative disorder with a heavy disease burden, despite the discovery and application of drugs. Current research is beginning to suggest the possible crucial roles of micronutrients such as pyridoxal phosphate in the prevention or management of neurodegenerative disorders. OBJECTIVE: We investigated the possible protective effects of supplemental pyridoxal phosphate in Chlorpromazine (CPZ)-induced Parkinsonism-like changes in mice. METHODS: Mice were assigned to eight groups of 30 mice each. Groups included Vehicle control (fed standard diet (SD), and administered intraperitoneal {ip} injection of saline and saline per orem), levodopa-carbidopa (LD) group (SD, saline ip and LD per orem), two groups fed pyridoxal phosphate-supplemented diet (at 100 and 200 mg/kg of feed), and administered saline both ip and orally, CPZ group (SD, CPZ ip and saline per orem), CPZ/LD group (SD, CPZ ip and LD per orem) and finally two groups fed pyridoxal phosphate -supplemented diet (at 100 and 200 mg/kg of feed) and administered CPZ ip plus saline per orem. Treatments were administered daily for a period of 21 days to allow for the induction of Parkinsonism features. Body weight and food intake were measured weekly while neurobehavioural and biochemical tests were assessed at the end of the experimental period. RESULTS: Pyridoxal phosphate supplementation was associated with a reduction in CPZ-induced suppression of open-field horizontal locomotion and rearing; and a significant increase in grooming activity. Administration of pyridoxal phosphate-supplemented diet was also associated with improvements in working-memory in CPZ-treated mice; and there was reduction in the index of anxiety and catalepsy score. CONCLUSION: Pyridoxal phosphate supplementation was associated with significant benefits in CPZ-induced Parkinsonism-like changes in mice.

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.

Melatonin in drug addiction and addiction management: Exploring an evolving multidimensional relationship.

Melatonin is a pleiotropic signalling molecule that regulates several physiological functions, and synchronises biological rhythms. Recent evidences are beginning to reveal that a dysregulation of endogenous melatonin rhythm or action may play a larger role in the aetiology and behavioural expression of drug addiction, than was previously considered. Also, the findings from a number of animal studies suggest that exogenous melatonin supplementation and therapeutic manipulation of melatonin/melatonin receptor interactions may be beneficial in the management of behavioural manifestations of drug addiction. However, repeated exogenous melatonin administration may cause a disruption of its endogenous rhythm and be associated with potential drawbacks that might limit its usefulness. In this review, we examine the roles of melatonin and its receptors in addictive behaviours; discussing how our understanding of melatonin's modulatory effects on the brain rewards system and crucial neurotransmitters such as dopamine has evolved over the years. Possible indications(s) for melatonergic agents in addiction management, and how manipulations of the endogenous melatonin system may be of benefit are also discussed. Finally, the potential impediments to application of melatonin in the management of addictive behaviours are considered.

Melatonin attenuates behavioural deficits and reduces brain oxidative stress in a rodent model of schizophrenia.

Melatonin is a neurohormone that is linked to the aetiopathogenesis of schizophrenia. The aim of this study was to assess the potentials of oral melatonin supplement in the management of induced schizophrenia-like behavioural and brain oxidative status changes, using an animal model. The relative degrees of modulation of ketamine-induced behaviours by haloperidol, olanzapine or melatonin were assessed in the open-field, Y-maze, elevated plus maze and the social interaction tests. 12-week old, male mice were assigned to six groups of ten each (n=10). They were pretreated with daily intraperitoneal ketamine at 15mg/kg (except vehicle) for 10days, before commencement of 14day treatment with standard drug (haloperidol or olanzapine) or melatonin. Ketamine injection also continued alongside melatonin or standard drugs administration for the duration of treatment. Melatonin, haloperidol and olanzapine were administered by gavage. Treatments were given daily, and behaviours assessed on days 11 and 24. On day 24, animals were sacrificed and whole brain homogenates used for the estimation of glutathione, nitric oxide and malondialdehyde levels. Ketamine injection increased open-field behaviours; while it decreased working-memory, social-interaction and glutathione activity. Nitric oxide and malondialdehyde levels also increased after ketamine injection. Administration of melatonin was associated with variable degrees of reversal of these effects. In conclusion, melatonin may have the potential of a possible therapeutic agent and/or adjunct in the management of schizophrenia.