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L-DOPA, the gold standard for managing Parkinson’s disease (PD) is fraught by motor fluctuations termed L-Dopa-Induced Dyskinesia (LID). LID has very few therapeutic options. Hence, the need for preclinical screening of new interventions. Cholecalciferol (VD3) treatment reportedly improves motor deficit in experimental Parkinsonism. Therefore, the novel anti-dyskinetic effect of VD3 and its underlying mechanisms in LID was investigated. Dyskinesia was induced by chronic L-DOPA administration in parkinsonian (6-OHDA- lesioned) mice. The experimental groups: Control, Dyskinesia, Dyskinesia/VD3, and Dyskinesia/Amantadine were challenged with L-DOPA to determine the abnormal involuntary movements (AIMs) score during 14 days of VD3 (30 mg/kg) or Amantadine (40 mg/kg) treatment. Behavioral Axial, Limb & Orolingual (ALO) AIMs were scored for 1 min at every 20 mins interval, over a duration of 100 mins on days 1,3,7,11 and 14. Using western blot, striatum was assessed for expression of dopamine metabolic enzymes: Tyrosine Hydroxylase (TH) and Monoamine Oxidase-B (MAO-B); CD11b, BAX, P47phox, and IL-1β. Cholecalciferol significantly attenuated AIMs only on days 11 & 14 with maximal reduction of 32.7%. Expression of TH and MAO-B was not altered in VD3 compared with dyskinetic mice. VD3 significantly inhibited oxidative stress (P47phox), apoptosis (BAX), inflammation (IL-1β) and microglial activation (CD11b). VD3 showed anti-dyskinetic effects behaviorally by attenuating abnormal involuntary movements, modulation of striatal oxidative stress, microglial responses, inflammation, and apoptotic signaling; without affecting dopamine metabolic enzymes. Its use in the management of dyskinesia is promising. More studies are required to further evaluate these findings. Keywords: Cholecalciferol; L-DOPA-Induced Dyskinesia; Parkinson’s Disease; Microglial; Oxidative stress; Inflammation

BACKGROUND: L-DOPA, the predominant therapy for Parkinson’s disease (PD) is associated with motor deficits after prolonged use. The nigrostriatal tract, a primary target of neurodegeneration in PD, contains abundant Vitamin-D receptors, suggesting a potential role for VD in the disease. Therefore, we tested the impact of Vitamin D(3) (V(3)) in a mouse model of PD. METHODS: PD was induced in adult male C57BL6 mice by a single intrastriatal injection of 6-hydroxydopamine. Two weeks post lesion, these mice received injections of a vehicle, VD(3), L-DOPA, or a combination of VD(3)/L-DOPA and compared with sham controls. Treatment lasted three weeks, during which motor-cognitive neurobehaviour was assessed. Five weeks post lesion, brains were collected and striatal levels of the following proteins assessed: tyrosine hydroxylase (TH), dopamine decarboxylase (DDC), monoamine oxidase (MAO-B), Catechol-O-methyl transferase (COMT), dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), microglia marker (CD11b), inflammation (IL-1β), apoptotic signaling (BAX) and oxidative stress (p47phox). RESULTS: Treatment with VD(3) attenuated behavioural deficits induced by 6-OHDA, protein associated with dopamine metabolism and biomarkers of oxidative stress. VD(3) significantly increased contralateral wall touches, exploratory motor and cognitive activities. VD(3) significantly enhanced the expression of TH, DAT, BDNF, while significantly reducing expression of MAO-B, CD11b, IL-I β and p47phox. CONCLUSION: VD(3) reversed some of the 6-OHDA induced changes in proteins involved in modulating the dopamine system, behavioural deficits and oxidative stress biomarkers. The data suggests that VD(3) might be beneficial in reducing L-DOPA dosage, thereby reducing problems associated with dosage and prolonged use of L-DOPA in PD management.

The potential of Se to alleviate pain associated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity was investigated. Swiss mice were intraperitoneally injected with MPTP (20 mg/kg) 4 times with an interval of 2 h in 1 day. Seven days after MPTP injection, the mice (n = 5 mice per group) were randomly assigned to groups: MPTP-, DOPA (50 mg/kg)-, Se4 (0.4 mg/kg)-, Se6 (0.6 mg/kg)-, DOPA+Se4-, and DOPA+Se6-treated groups were compared with controls. MPTP mice were treated for seven days; thereafter, motor-coordination and nociceptive-motor reactions were assessed. Pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and selected pain biomarkers (substance P (SP), glutamate and β-endorphin) were assessed in the serum and the substantial nigra pars compacta (SNpc). Motor activity was increased slightly by Se (0.6 or 0.4 mg/kg) vs. MPTP (10.48 ± 2.71 or 11.81 ± 1.28 s vs. 3.53 ± 0.06 s respectively) but considerably increased by DOPA (50 mg/kg) vs. MPTP (50.47 ± 3.06 s vs. 3.53 ± 0.06 s respectively). Se and DOPA increased nociceptive threshold but Se alone reduced both serum and SN pro-inflammatory cytokines. Se modulates SP while DOPA modulates SP and glutamate in the SNpc of mice treated with MPTP. Se suppressed pro-inflammatory cytokines and restored the basal pain biomarkers in the SNpc of mice treated with MPTP. Se requires further study as analgesic adjuvant.

ObjectiveThe metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis.MethodsWe used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology.ResultsADAM17adipoq-creΔ/Δmice exhibited a hypermetabolic phenotype characterized by elevated energy consumption and increased levels of adipocyte thermogenic gene expression. On a high fat diet, these mice were more thermogenic, while exhibiting elevated expression levels of genes associated with lipid oxidation and lipolysis. This hypermetabolic phenotype protected mutant mice from obesogenic challenge, limiting weight gain, hepatosteatosis and insulin resistance. Activation of beta-adrenoceptors by the neurotransmitter norepinephrine, a key regulator of adipocyte physiology, triggered the shedding of ADAM17 substrates, and regulated ADAM17 expression at the mRNA and protein levels, hence identifying a functional connection between thermogenic licensing and the regulation of ADAM17. Proteomic studies identified Semaphorin 4B (SEMA4B), as a novel ADAM17-shed adipokine, whose expression is regulated by physiological thermogenic cues that acts to dampen thermogenic responses in adipocytes. Transcriptomic data showed that cleaved SEMA4B acts in an autocrine manner in brown adipocytes to dampen the expression of genes involved in thermogenesis, adipogenesis, lipid uptake, storage and catabolism.ConclusionOur findings identify a novel ADAM17-dependent axis, regulated by beta-adrenoceptors and mediated by the ADAM17-cleaved form of SEMA4B, that may act to limit uncontrolled energy depletion during thermogenesis.

The 'Crosstalks of immunity and metabolism' Symposium was focused on how the intercommunication between different organs and the immune system affects organismal health. At this meeting, experts in immunology and metabolic research provided novel insights into the growing field of immunometabolism. This report attempts to review and integrate views, ideas, propositions, and conclusions that emanated from the symposium.

The metalloprotease ADAM17 catalyzes the shedding of key signalling molecules from the cell surface, including the inflammatory cytokine TNF (tumour necrosis factor) and activating ligands of the EGFR (epidermal growth factor receptor). ADAM17 exists within an assemblage called the “sheddase complex” containing a rhomboid pseudoprotease (iRhom1 or iRhom2). iRhoms control multiple aspects of ADAM17 biology, including its vesicular trafficking, maturation from its precursor pro-form, activation on the cell surface and specificity for subsets of proteolytic targets. Previous studies from our laboratory and others identified the FERM domain-containing protein Frmd8/iTAP as an iRhom-binding protein. iTAP is required to maintain the cell surface stability of the sheddase complex, thereby preventing the precocious shunting of ADAM17 and iRhom2 to lysosomes and their consequent degradation. As pathophysiological role(s) of iTAP have not been addressed, here we sought to characterize the impact of loss of iTAP on ADAM17-associated phenotypes in mice. Our data show that iTAP KO mice exhibit defects in ADAM17 activity in inflammatory and intestinal epithelial barrier repair functions, but do not exhibit the collateral effects associated with global loss of ADAM17. Furthermore, we show that iTAP promotes cancer cell growth in a cell-autonomous manner, and by modulating the tumor microenvironment. Our work suggests that pharmacological intervention at the level of iTAP may be beneficial to target ADAM17 activity in specific compartments during chronic inflammatory diseases or cancer, avoiding the deleterious impact on vital functions associated with the widespread inhibition of ADAM17 in normal tissues.

The metalloprotease ADAM17 is a sheddase of key molecules, including TNF and epidermal growth factor receptor ligands. ADAM17 exists within an assemblage, the “sheddase complex,” containing a rhomboid pseudoprotease (iRhom1 or iRhom2). iRhoms control multiple aspects of ADAM17 biology. The FERM domain–containing protein iTAP/Frmd8 is an iRhom-binding protein that prevents the precocious shunting of ADAM17 and iRhom2 to lysosomes and their consequent degradation. As pathophysiological role(s) of iTAP/Frmd8 have not been addressed, we characterized the impact of iTAP/Frmd8 loss on ADAM17-associated phenotypes in mice. We show that iTAP/Frmd8 KO mice exhibit defects in inflammatory and intestinal epithelial barrier repair functions, but not the collateral defects associated with global ADAM17 loss. Furthermore, we show that iTAP/Frmd8 regulates cancer cell growth in a cell-autonomous manner and by modulating the tumor microenvironment. Our work suggests that pharmacological intervention at the level of iTAP/Frmd8 may be beneficial to target ADAM17 activity in specific compartments during chronic inflammatory diseases or cancer, while avoiding the collateral impact on the vital functions associated with the widespread inhibition of ADAM17.

L-DOPA Induced Dyskinesia (LID) is associated with prolonged L-DOPA therapy. Vitamin-D receptor modulation improves motor-cognitive deficit in experimental LID Parkinsonism. Therefore, in this study, we investigated the mechanism underlying the anti-dyskinetic potential of Vitamin D3 (VD3). Dyskinesia was induced by chronic L-DOPA administration in 6-OHDA lesioned male C57BL6 mice. The experimental groups (Dyskinesia, Dyskinesia/VD3, and Dyskinesia/Amantadine) and controls were challenged with L-DOPA to determine the abnormal involuntary movements (AIMs) score during 14 days of VD3(30 mg/kg) or Amantadine (40 mg/kg) treatment. Global behavioral Axial, Limb & Orolingual (ALO) AIMs were scored for 1 min at every 20 mins interval, over a duration of 100 mins on days 1,3,7,11 and 14 of treatment. Thereafter, brain samples were collected and processed for immunoblotting to assess striatal expression of tyrosine hydroxylase (TH), monoamine oxidase (MAO), cathecol-o-methyl transferase (COMT), dopamine decarboxylase (DDC), CD11b, BAX, P47phox, and IL-1β. VD3significantly attenuated ALO AIMs only on days 11 & 14, with maximal reduction of 32.7% compared with dyskinetic mice but had no effect on days 1, 3 & 7, while amantadine decreased AIMs all through days 1 to 14 with maximal reduction of 64.5%. TH and MAO-B expression were not significantly different across the groups. DDC was significantly suppressed in dyskinetic micevscontrol (p3micevsdyskinetic mice. COMT was upregulated in the dyskinetic groupvscontrol (p3mice (p3inhibited significantly (p3is associated with modulation of striatal oxidative stress, microglial responses, inflammation, and apoptotic signaling.Impact statementThere are evidences showing that VD3supplementation improves motor disorders, including Parkinson’s disease. We hypothesized that VD3could improve LID, an abnormal involuntary movement that results from prolonged L-DOPA therapy in the management of PD. We have demonstrated the novel anti-dyskinetic effect of VD3and associated mechanistic factors in a mouse model of L-DOPA Induced Dyskinesia (LID), which identifies promising targets for dyskinesia therapy.

Objective Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome. Methods We challenged WT versus iRhom2 KO mice to positive energy balance by chronic exposure to a high fat diet and then compared their metabolic phenotypes. We also carried out ex vivo assays with primary and immortalized mouse brown adipocytes to establish the autonomy of the effect of loss of iRhom2 on thermogenesis and respiration. Results Deletion of iRhom2 protected mice from weight gain, dyslipidemia, adipose tissue inflammation, and hepatic steatosis and improved insulin sensitivity when challenged by a high fat diet. Crucially, the loss of iRhom2 promotes thermogenesis via BAT activation and beige adipocyte recruitment, enabling iRhom2 KO mice to dissipate excess energy more efficiently than WT animals. This effect on enhanced thermogenesis is cell-autonomous in brown adipocytes as iRhom2 KOs exhibit elevated UCP1 levels and increased mitochondrial proton leak. Conclusion Our data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasis during metabolic disease., Highlights • Deletion of iRhom2 protects mice from metabolic syndrome. • In obesity, iRhom2 deletion increases energy expenditure, thermogenesis and white adipose tissue beiging. • iRhom2 deletion enhances thermogenesis in naïve brown adipocytes.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis in insulin-secreting beta-cells is essential. Several pathophysiological conditions and pharmacological agents disrupt the ER homeostasis, thereby causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways whenever the ER stress persists. ER stress has been linked to several diseases, such as cancers, obesity, and diabetes. Thus, the regulation of ER stress may provide possible therapeutic targets for many diseases. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, resulting in irreversible UPR activation and cells death. Despite much progress in understanding the pathophysiology of UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provided up-to-date information regarding the current status of UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Neuroscience research in Africa remains sparse. Devising new policies to boost Africa’s neuroscience landscape is imperative, but these must be based on accurate data on research outputs which is largely lacking. Such data must reflect the heterogeneity of research environments across the continent’s 54 countries. Here, we analyse neuroscience publications affiliated with African institutions between 1996 and 2017. Of 12,326 PubMed indexed publications, 5,219 show clear evidence that the work was performed in Africa and led by African-based researchers - on average ~5 per country and year. From here, we extract information on journals and citations, funding, international coauthorships and techniques used. For reference, we also extract the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our dataset provides insights into the current state of African neuroscience research in a global context., Here, the authors survey neuroscience publications from Africa over the past two decades, highlighting areas of active research, international networks, funding, and techniques used.

Nature and size of rodent cages vary from one laboratory or country to another. Little is however known about the physiological implications of exposure to diverse cage sizes in animal-based experiments.Here, two groups of male Swiss mice (Control group - Cage stationed, and Test group - Cage migrated) were used for this study. The cage-migrated mice were exposed daily to various cage sizes used across laboratories in Nigeria while the cage-stationed mice exposed daily to different but the same cage size and shape. At the end of the 30 days exposure, top-rated paradigms were used to profile changes in physiological behaviours, and this was followed by evaluation of histological and biochemical metrics.The study showed a significant (p 0.05) decrease in blood glucose levels (at 60 and 120 min of oral glucose tolerance test) in the cage-migrated mice compared to cage-stationed mice. Strikingly, peripheral oxidative stress (plasma malondialdehyde) and pain sensitivity (formalin test, hot-and-cold plate test, and von Frey test) decreased significantly in cage-migrated mice compared to cage-stationed animals. Also, the pro-inflammation mediators (IL-6 and NF-κB) increased significantly in cage-migrated mice compared to cage-stationed mice. However, emotion-linked behaviours, neurotransmitters (serotonin, noradrenaline and GABA), brain and plasma electrolytes were not significantly difference in cage-migrated animals compared to cage-stationed mice.Taken together, these results suggest that varied size cage-to-cage exposure of experimental mice could affect targeted behavioural and biomolecular parameters of pain and inflammation, thus diminishing research reproducibility, precipitating false negative/positive results and leading to poor translational outcomes.

Background: The emergence of a multidrug-resistant strain of Plasmodium falciparum (Pf Pailin) raises concern about malaria control strategies. Unfortunately, the role(s) of natural plants...

Background: There has been a rise in accidental poisoning cases resulting from the indiscriminate use and exposure to Dichlorvos (DDVP), especially in developing countries, and no antidote with satisfactory efficacy is currently available. Thus, we investigated the AChE reactivation potential of Nigella sativa oil (NSO) following DDVP induced AChE inhibition patterns in the brain and the associated cognitive implications. Methods: Fourty Wistar rats were randomly divided into four groups of 10 each.; The controls were administered PBS (1 ml/kg); DDVP (8.8 mg/kg) was given to the experimental group I; while DDVP+NSO (8.8 mg/kg + 1 ml/kg) and NSO (1 ml/kg) was administered orally to the experimental groups II and III respectively. All treatments lasted for 14 consecutive days. Morris Water Maze (MWM) paradigm was used to assess the working memory, then rats were euthanized, the brain excised, three brains were fixed for histological examination (Nissl staining), and the other seven brains were homogenized for AChE activity and Ca2+ concentrations. Data were analyzed statistically, using ANOVA method and P values of ≤0.05 was considered as significant. Results: In this study, DDVP differentially inhibited AChE activities in various brain regions: cerebellum (86.1%), hippocampus (40.6%), frontal cortex (33.2%), medulla (21.5%), spinal cord (14.8%), and occipital cortex (8.9%). It reduced Ca2+ concentration, but had no effect on the delayed escape latency in the MWM, nor impaired the neuro-architectures. NSO caused increased AChE activities, Ca2+ concentration and reduced escape latency, and improved histologic architectures. Conclusion: We concluded that NSO reactivated DDVP-induced AChE inhibition and improved memory indices, thus, it may serve as a potential treatment in the management of DDVP poisoning cases.

Africa is faced with an increasing underrepresentation of her research progress in many fields of science including neuroscience. This underrepresentation stems from the very low investments directed towards research by African governments as these are thought to be high-priced. Scientists and researchers within the continent are left to compete highly for the very limited research grants or choose to fund research from their personal purse. Therefore, presenting a need for all possible strategies to make science and research approaches more affordable in Africa. This paper presents one of such strategy, which advocates the use of invertebrate animal models for neuroscience research in place of the commonly used vertebrate models. Invertebrates are cheaper, more available and easy to handle options and their use is on the rise, even in the developed societies of the world. Here, we investigate the current state of invertebrate neuroscience research in Africa looking at countries and institutions conducting neuroscience research with invertebrates and their publication output. We discuss the factors which impede invertebrate neuroscience research in Africa like lack of research infrastructure and adequate expert scientists and conclude by suggesting solutions to these challenges.

Objective:Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energydissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Herewe evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in thepathophysiology of metabolic syndrome.Methods:We challenged WT versus iRhom2 KO mice to positive energy balance by chronic exposure to a high fat diet and then compared theirmetabolic phenotypes. We also carried outex vivoassays with primary and immortalized mouse brown adipocytes to establish the autonomy ofthe effect of loss of iRhom2 on thermogenesis and respiration.Results:Deletion of iRhom2 protected mice from weight gain, dyslipidemia, adipose tissue inflammation, and hepatic steatosis and improvedinsulin sensitivity when challenged by a high fat diet. Crucially, the loss of iRhom2 promotes thermogenesis via BAT activation and beigeadipocyte recruitment, enabling iRhom2 KO mice to dissipate excess energy more efficiently than WT animals. This effect on enhanced ther-mogenesis is cell-autonomous in brown adipocytes as iRhom2 KOs exhibit elevated UCP1 levels and increased mitochondrial proton leak.Conclusion:Our data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasisduring metabolic disease, Wellcome Trust strategic award (100574/Z/12/Z) and MRC MDU (MC_UU_12012/2

Background Nature and size of rodent cages vary from one laboratory or country to another. Little is however known about the physiological implications of exposure to diverse cage sizes in animal-based experiment. Here, we exposed male Swiss mice to various cage sizes used across laboratories in Nigeria, top-rated paradigms were used to profile changes in physiological behaviours, and this was followed by evaluation of modified biochemical metrics. Results The study showed a better systemic regulation of glucose metabolism in cage migrated mice compared to cage stationed. Strikingly, peripheral oxidative stress and pain sensitivity decreased significantly in cage-to-cage migrated mice despite increased pro-inflammation mediators (IL-6 and NF-κB) which contrast the norm reported in inflammatory conditions. Interestingly, emotion-linked behaviours, neurotransmitters (serotonin, noradrenaline and GABA) and body electrolytes were not altered by cage-to-cage migration. Conclusion Taken together, these results suggest that varied size cage-to-cage migration of experimental mice could affect targeted behavioural and biomolecular parameters of pain and inflammation, thus diminishing research reproducibility, precipitating false negative/positive results and leading to poor translational outcomes.

Understanding the function and dysfunction of the brain remains one of the key challenges of our time. However, an overwhelming majority of brain research is carried out in the Global North, by a minority of well-funded and intimately interconnected labs. In contrast, with an estimated one neuroscientist per million people in Africa, news about neuroscience research from the Global South remains sparse. Clearly, devising new policies to boost Africa’s neuroscience landscape is imperative. However, the policy must be based on accurate data, which is largely lacking. Such data must reflect the extreme heterogeneity of research outputs across the continent’s 54 countries distributed over an area larger than USA, Europe and China combined. Here, we analysed all of Africa’s Neuroscience output over the past 21 years. Uniquely, we individually verified in each of 12,326 publications that the work was indeed performed in Africa and led by African-based researchers. This step is critical: previous estimates grossly inflated figures, because many of Africa’s high-visibility publications are in fact the result of internationally led collaborations, with most work done outside of Africa. The remaining number of African-led Neuroscience publications was 5,219, on average only ~5 per country and year. From here, we extracted metrics such as the journal and citations, as well as detailed information on funding, international collaborations and the techniques and model systems used. We link these metrics to demographic data and indicators of mobility and economy. For reference, we also extracted the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our unique dataset allows us to gain accurate and in-depth information on the current state of African Neuroscience research, and to put it into a global context. This in turn allows us to make actionable recommendations on how African research might best be supported in the future.

This study was conducted to evaluate cognitive enhancing effect and ameliorative effects of black seed oil in scopolamine induced rat model of cognitive impairment. These effects were investigated on scopolamine-induced dementia model in Morris water maze test (MWM) and Y maze test. The hippocampal histoarchitectural responses to scopolamine and Nigella sativa oil were also examined. Scopolamine (1 mg/kg ip) was given to induce dementia, followed by oral administration of BSO (1 ml/kg) for 14 consecutive days. MWM and Y-maze paradigms were used to assess hippocampal and frontal dependent memory respectively, thereafter the rats were sacrificed and brains were removed for histopathologic studies. Scopolamine resulted in memory impairment, by delayed latency in the MWM, reduced percentage alternation in the Y maze that was coupled by alterations in the cortico-hippocampal neurons. Posttreatment of rats with BSO mitigated scopolamine-induced amnesia, by reducing latency period and increasing percentage alternation and histological changes. The observed anti-amnestic effect of BSO makes it a promising anti-amnesic agent for clinical trials in patients with cognitive impairment.

Background: The emergence of a multidrug-resistant strain of Plasmodium falciparum (Pf Pailin) raises concern about malaria control strategies. Unfortunately, the role(s) of natural plants/remedies in curtailing malaria catastrophe remains uncertain. The claims of potential antimalarial activity of Cannabis sativa in vivo have not been well established nor the consequences defined. This study was, therefore, designed to evaluate the effects of whole cannabis consumption on malaria-infected host. Methods: Thirty mice were inoculated with dose of 1×107 chloroquine-resistant Plasmodium berghei ANKA-infected erythrocyte and divided into six treatment groups. Cannabis diet formulations were prepared based on weighted percentages of dried cannabis and standard mice diet and the study animals were fed ad libitum. Chemosuppression of parasitemia, survival rates, parasite clearance, and recrudescence time were evaluated. Histopathological studies were performed on the prefrontal cortex (PFC) and hippocampus of the animals after 14 days' consumption of cannabis diet formulation by naive mice. Results: There was a significant difference (p

This research sought to investigate the possible neuroprotective effects of honey against lead (Pb)-induced neurotoxicity. Twenty four male Wistar rats were divided into four groups: Control group that received 1 ml/kg distilled orally for 28 days; while groups II-IV received 0.2% lead in drinking water and 1 ml/kg of distilled water, 1 ml/kg of honey, 1.5 ml/kg of honey respectively for 28 days. Anxiety and exploratory activities were determined in the open field test. Memory function was determined using Morris water maze after which the animals were sacrificed. The brains were then excised, homogenized and Lipid peroxidation (MDA), Superoxide dismutase (SOD), Catalase, Glutathione (GSH) and Glutathione -S- Transferase (GST) activities were determined in the brains. Results showed that lead exposure causes decrease in locomotor and exploratory activities; increase anxiety, memory impairment, lipid peroxidation and decrease antioxidant activities. However, co-administration of honey with lead inhibited neurotoxicity as indicated by the improvement in memory function as evidenced by decreased latency period and increased in time spent in target quadrant in honey-fed rats compared to the lead-exposed animals. Furthermore, honey increased locomotion, exploration and decreased anxiety in lead-exposed rats as indicated by the frequency of rearing, freezing duration and the number of line crossed by animals. Also administration of honey improves antioxidant activities as shown by increased brain SOD, GST and GSH activities compared to the lead-treated groups but no significant effect on MDA level. It can be concluded that honey has neuroprotective effects against lead-induced cognitive deficit probably by enhancing antioxidant activities.

Objective: Increased oxidative stress is associated with the progression of diabetic mellitus. In the present study, we investigated the effects of the ethanolic extract of Nigerian propolis (N. propolis) on markers of oxidative stress, histology of the liver and pancreas and glycaemia in alloxan-induced diabetic rats. Materials and Methods: Alloxan-induced hyperglycaemic Wistar rats were treated with either metformin (150mg/kg/d) or N. propolis (200mg/kg/d and 300mg/kg/d)) for 28 days. At the end of treatment period, the rats were sacrificed; blood was collected for biochemical analysis while their pancreases and liver were excised and processed for histological studies. Results: Serum oxidative stress markers and blood glucose concentration were compared between the treated and control rats. In contrast to the non-treated diabetic rats, blood glucose concentration were not significantly different between treated rats and control (P

The science of the brain and nervous system cuts across almost all aspects of human life and is one of the fastest growing scientific fields worldwide. This necessitates the demand for pragmatic investment by all nations to ensure improved education and quality of research in Neurosciences. Although obvious efforts are being made in advancing the field in developed societies, there is limited data addressing the state of neuroscience in sub-Saharan Africa. Here, we review the state of neuroscience development in Nigeria, Africa’s most populous country and its largest economy, critically evaluating the history, the current situation and future projections. This review specifically addresses trends in clinical and basic neuroscience research and education. We conclude by highlighting potentially helpful strategies that will catalyse development in neuroscience education and research in Nigeria, among which are an increase in research funding, provision of tools and equipment for training and research, and upgrading of the infrastructure at hand.

Neuroscience research and training in many African countries are difficult due to funding and infrastructure deficit. This has resulted in few neuroscientists within Africa. However, invertebrates such as Drosophila and Caenorhabditis elegans could provide the perfect answer to these difficulties. These organisms are cheap, easy to handle and offer a comparable advantage over vertebrates in neuroscience research modeling because they have a simple nervous system and exhibit well-defined behaviors. Studies using invertebrates have helped to understand neurosciences and the complexes associated with it. If Africa wants to catch up with the rest of the world in neuroscience research, it needs to employ this innovative cost-effective approach in its research. To improve invertebrate neuroscience within the Africa continent, the authors advocated the establishment of invertebrate research centers either at regional or national level across Africa. Finally, there is also a need to provide public funding to consolidate the gains that have been made by not-for-profit international organizations over the years.

Aim: The use of Azathioprine (AZA) in the prevention of organ rejection during transplantation has been documented for different organs of the body. In this study, we investigated the effects of azathioprine on the integrity of the testis of Wistar rats using histological and histochemical techniques. Methods: Eighteen adult male Wistar rats with mean weight 210±2.65 g were randomly assigned into three groups. Group I (control) received 1 ml of normal saline “per os” (p.o), group II animals received 10 mg/kg AZA (p.o) while group III animals received 20 mg/kg AZA (p.o). Treatment lasted for 21 days. Twenty-four hours after treatment, animals were sacrificed; their testes excised, weighed and fixed in Bouin’s fluid for histological evaluation using Haematoxylin and Eosin while histochemical studies were carried out using Gordon and Sweets, and Masson’s Trichrome staining techniques. Testicular homogenate was used to assay for testosterone level. Results: Treatment with Azathioprine reduced testosterone level while the histological and histochemical findings of the testicular sections revealed cyto-architectural distortions and reduced staining intensity of collagen and reticulin connective tissue fibers in AZA treated animals compared to the control group. Conclusion: Results from the study reveal that the immunosuppressive drugazathioprine when used at a concentration above 10 mg/kg disrupts the testicular integrity of adult Wistar rats. Keywords: Azathioprine, Testis, Collagen, Reticulin

Aim: Nigella sativa oil has been shown to improve metabolic syndrome-associated dyslipidemia and oxidative stress. Effects of N. sativa oil on letrozole-induced polycystic ovary syndrome (PCOS)-associated hormonal, metabolic, redox, and lipid dysregulation in rats were investigated. Methods: Female Sprague-Dawley rats were randomly assigned into four groups (n=10 per group): control, PCOS, and PCOS treated with N. sativa oil (5 mL/kg/day or 10 mL/kg/day) once daily p.o. starting at day 7 after the commencement of letrozole (1mg/kg) until day 56. Body weight and estrous cycle were recorded starting from days 7 and 28 respectively until day 56. Rats were dissected and serum and ovaries were collected for biochemical and histomorphological assessments. Results: N. sativa oil (10 mL/kg/day) treatment significantly increased: number of rats undergoing regular cycle (80% vs 20%; p< 0.05), average number of regular cycles (5.00±0.59 vs 0.20±0.42; p< 0.05), appearance of corpus luteum; but reduced number of cystic follicles (7.60±1.51 vs 6.10±0.19; p< 0.05) in PCOS rats. Body weight was also reduced by the oil in PCOS rats. However, ovarian weight, granulose and theca cells layers showed no significant change. The oil also restored altered circulating levels of gonadotropins, steroids and reduced fasting blood glucose. The ovarian total cholesterol, triglycerides, low density lipoprotein-cholesterol, malondialdehyde were markedly reduced while insulin sensitivity and ovarian high density lipoprotein-cholesterol, superoxide dismutase and glutathione peroxidase activities were greatly increased. Conclusion: N. sativa oil improved polycystic ovarian-morphology and metabolic disorders via its anti-androgenic and insulin-sensitizing actions to ameliorate PCOS-associated dyslipidemia and redox disturbances.

Background Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Methods Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Results Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. Conclusions The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

Objective: The study was designed to investigate the effects of continuous exposure of dichlorvos (DDVP) on hepatic function and hepatic histomorphology, with the possible antidotal efficacy of Nigella sativa oil (NSO). Methods: Twenty four Wistar rats were randomly divided into four groups, with each group comprising of six rats. The groups were labelled as Sunflower oil (SFO), DDVP, DDVP+NSO and NSO. After 14 days of treatments, blood samples were collected, centrifuged and levels of ALP (Alkaline phosphatase), ALT (Alanine aminotransferase), AST (Aspartate aminotransferase) and GGT (a-glutamyl-transferase) concentrations were estimated in the serum. The livers were removed and prepared for histopathological examinations and evaluation. Results: The findings of the study shows significant increase in the serum concentration of ALT, ALP, AST and GGT with a marked distortion in the hepatic architecture in rats administered with DDVP. However, Nigella sativa oil (NSO) was observed to ameliorate the levels of impairment in the assessed hepatic function parameters and relatively restoration in the hepatic architecture in DDVP+NSO treated animals when compared to the control and group administered with DDVPonly. Conclusion: The study concludes that impaired liver functions and histomorphological tissue distortions observed in the experimental rats following DDVP exposure were ameliorated following the administration of NSO.

The use of azathioprine (AZA) in the prevention of organ rejection during transplantation has been noted in different organs of the body. This study investigates the effect of ascorbic acid on azathioprineinduced alteration in the testes of adult Wistar rats. Thirty male adult Wistar rats were randomly assigned into 5 groups comprising a Control group A and four Treatment groups B to E. Animals in treatment groups B and D received 10 and 20 mg/kg of AZA respectively; while rats in treatment groups C received 10 mg/kg AZA + 25 mg/kg ascorbic acid, and group E received 20 mg/kg of AZA + 50 mg/kg of ascorbic acid. The control group animals received equal volume of normal saline via orogastric tube, and treatment lasted for 21 days. The testes were excised, weighed and fixed in Bouins’ fluid for tissue histology. Tissue homogenate was used to assay testosterone level, while blood was also obtained intracardially for glutathione peroxidase studies. Findings revealed significant histological changes in the treatment groups, decreased testosterone levels, and elevated glutathione peroxidase activity in all the treatment groups, compared with control. However, the treatment groups that received ascorbic acid had minimal, but significant reduction in the glutathione peroxidase activity compared to treatment groups without ascorbic acid intervention. Use of azathioprine induces significant damage to testicular structure, and this cannot be ameliorated by the use of ascorbic acid. Keywords : Ascorbic acid, azathioprine, glutathione peroxidase, testes, testosterone.