Black seed oil reverses chronic antibiotic-mediated depression and social behaviour deficits via modulation of hypothalamic mitochondrial-dependent markers and insulin expression.

Chronic antibiotic use has been reported to impair mitochondrial indices, hypothalamus-mediated metabolic function, and amygdala-regulated emotional processes. Natural substances such as black seed (Nigella sativa) oil could be beneficial in mitigating these impairments. This study aimed to assess the impact of black seed oil (NSO) on depression and sociability indices, redox imbalance, mitochondrial-dependent markers, and insulin expression in mice subjected to chronic ampicillin exposure. Forty adult male BALB/c mice (30 ± 2 g) were divided into five groups: the CTRL group received normal saline, the ABT group received ampicillin, the NSO group received black seed oil, the ABT/NSO group concurrently received ampicillin and black seed oil, and the ABT+NSO group experienced pre-exposure to ampicillin followed by subsequent treatment with black seed oil. The ampicillin-exposed group exhibited depressive-like behaviours, impaired social interactive behaviours, and disruptions in mitochondrial-dependent markers in plasma and hypothalamic tissues, accompanied by an imbalance in antioxidant levels. Moreover, chronic antibiotic exposure downregulated insulin expression in the hypothalamus. However, these impairments were significantly ameliorated in the ABT/NSO, and ABT+NSO groups compared to the untreated antibiotic-exposed group. Overall, findings from this study suggest the beneficial role of NSO as an adjuvant therapy in preventing and abrogating mood behavioural and neural-metabolic impairments of chronic antibiotic exposure.

Tiger nut/coconut dietary intervention as antidotal nutritional remediation strategy against neurobehavioural deficits following organophosphate-induced gut-brain axis dysregulation in mice.

Organophosphate poisoning remains a global health crisis without efficacious treatments to prevent neurotoxicity. We examined whether antidotal tiger nut and coconut dietary intervention could ameliorate neurobehavioral deficits from organophosphate dichlorvos-induced gut-brain axis dysregulation in a mouse model. Mice were divided into groups given control diet, dichlorvos-contaminated diets, or dichlorvos plus nut-enriched diets. They were exposed to a DDVP-contaminated diet for 4 weeks before exposure to the treatment diets for another 8 weeks. This was followed by behavioural assessments for cognitive, motor, anxiety-, and depressive-like behaviours. Faecal samples (pre- and post-treatment), as well as blood, brain, and gut tissues, were collected for biochemical assessments following euthanasia. Dichlorvos-exposed mice displayed impairments in cognition, motor function, and mood along with disrupted inflammatory and antioxidant responses, neurotrophic factor levels, and acetylcholinesterase activity in brain and intestinal tissues. Weight loss and altered short-chain fatty acid levels additionally indicated gut dysfunction. However, intervention with tiger nut and/or coconut- enriched diet after dichlorvos exposure attenuated these neurobehavioral, and biochemical alterations. Our findings demonstrate organophosphate-induced communication disruptions between the gut and brain pathways that manifest in neuropsychiatric disturbances. Overall, incorporating fibre-rich nuts may represent an antidotal dietary strategy to reduce neurotoxicity and prevent brain disorders associated with organophosphate poisoning.

Neurobehavioral deficits, histoarchitectural alterations, parvalbumin neuronal damage and glial activation in the brain of male Wistar rat exposed to Landfill leachate.

Concerns about inappropriate disposal of waste into unsanitary municipal solid waste landfills around the world have been on the increase, and this poses a public health challenge due to leachate production. The neurotoxic effect of Gwagwalada landfill leachate (GLL) was investigated in male adult Wistar rats. Rats were exposed to a 10% concentration of GLL for 21 days. The control group received tap water for the same period of the experiment. Our results showed that neurobehavior, absolute body and brain weights and brain histomorphology as well as parvalbumin interneurons were severely altered, with consequent astrogliosis and microgliosis after 21 days of administrating GLL. Specifically, there was severe loss and shrinkage of Purkinje cells, with their nucleus, and severe diffused vacuolations of the white matter tract of GLL-exposed rat brains. There was severe cell loss in the granular layer of the cerebellum resulting in a reduced thickness of the layer. Also, there was severe loss of dendritic arborization of the Purkinje cells in GLL-exposed rat brains, and damage as well as reduced populations of parvalbumin-containing fast-spiking GABAergic interneurons in various regions of the brain. In conclusion, data from the present study demonstrated the detrimental effects of Gwagwalada landfill leachate on the brain which may be implicated in neuropsychological conditions.

Prolonged ketamine therapy differentially rescues psychobehavioural deficits via modulation of nitro-oxidative stress and oxytocin receptors in the gut-brain-axis of chronically-stressed mice.

Ketamine is an anaesthetic known to have short but rapid-acting anti-depressant effects; however, the neurobehavioural effects of its prolonged use and its role on the oxytocin system in the gut-brain axis are largely undetermined. Female BALB/c mice were either exposed to the chronic unpredictable mild stress (CUMS) paradigm for 21 days and then treated with ketamine in four doses for 14 days or exposed to CUMS and treated simultaneously in four doses of ketamine during the last two weeks of CUMS exposure. After each dose, the forced swim test was conducted to assess depressive-like behaviour. Before sacrifice, all the mice were subjected to behavioural tests to assess anxiety, memory, and social interaction. Prolonged treatment of depression with ketamine did not rescue depressive-like behaviour. It did, however, improve depression-associated anxiety-like behaviours, short-term memory and social interaction deficits when compared to the stressed untreated mice. Furthermore, ketamine treatment enhanced plasma oxytocin levels, expression of oxytocin receptors; as well as abrogated nitro-oxidative stress biomarkers in the intestinal and hippocampal tissues. Taken together, our findings indicate that while short-term use of ketamine has anti-depressant benefits, its prolonged therapeutic use does not seem to adequately resolve depressive-like behaviour in mice.

Quercetin abrogates lipopolysaccharide-induced depressive-like symptoms by inhibiting neuroinflammation via microglial NLRP3/NFκB/iNOS signaling pathway.

BACKGROUND: Major depressive disorder is a serious psychiatric illness having serious damaging effect on the quality of life of suffers. Quercetin is a plant flavonoid, mostly used as a constituent in dietary products. This study evaluated antidepressant effect of quercetin on lipopolysaccharide (LPS)-induced depression in rats. MATERIALS AND METHODS: Twenty-one male rats were randomly assigned into three groups (n = 7): group 1 (vehicle only), group 2 (quercetin), group 3 (LPS). Rats were treated with vehicle (10 mL/kg, p.o.) or quercetin (50 mg/kg, p.o.) for seven days. Sixty minutes after treatment on day seven, all animals were injected with LPS (0.83 mg/kg, i.p.) except group 1 (vehicle only). Twenty-four hours after LPS injection, animals were assessed for depressive symptoms using forced swim, sucrose splash and open field tests. Animals were sacrificed; brain samples collected for bioassay of pro-inflammatory mediators, TNF-α, IL-6 and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA) while expressions of NF-κB, inflammasomes, microglia and iNOS were quantified by immunohistochemistry. RESULTS: The LPS significantly (p < 0.05) decreased mobility of rats in FST and decreased sucrose preference, which is indicative of depressive-like behaviours. These behaviours were significantly (p < 0.05) attenuated by quercetin compared to control (vehicle only). Following LPS exposure, the expressions of inflammasomes, NF-κB, iNOS, proinflammatory cytokines and microglia positive cells in the hippocampus and prefrontal cortex were significantly (p < 0.05) elevated. All these were attenuated by pretreating animals with quercetin. CONCLUSION: Quercetin exhibit antidepressant-like property, which may be related to inhibition of neuroinflammatory signaling pathways.

Ketamine abrogates sensorimotor deficits and cytokine dysregulation in a chronic unpredictable mild stress model of depression.

Major depressive disorder (MDD) is a serious mental disorder with influence across the functional systems of the body. The pathogenesis of MDD has been known to involve the alteration of normal body functions responsible for the normal inflammation processes within the CNS; this along with other effects results in the depreciation of the sensorimotor performance of the body. Ketamine hydrochloride, a novel antidepressant agent, has been used as a therapeutic agent to treat MDD with its efficacy stretching as far as enhancing sensorimotor performance and restoring normal cytokine levels of the CNS. While these therapeutic actions of ketamine may or may not be related, this study made use of chronic unpredictable mild stress (CUMS) to generate the mouse model of depression. The efficacy of ketamine as an antidepressant following sequential exposure and co-administrative treatment protocols of administration was evaluated using behavioural tests for sensorimotor performance and depressive-like behaviours. Its effect in managing CNS inflammation was assessed via the biochemical analysis of inflammatory cytokine levels in the cerebrum, spinal cord and cerebellum; and immunohistochemical demonstration of microglial activity in the corpus striatum and cerebellum. The sensorimotor performance which had been diminished by CUMS showed greater improvement under the sequential exposure regimen of ketamine. Ketamine was also efficacious in decreasing the level of inflammation with an evident reduction in microglial activation and pro-inflammatory cytokines in the studied regions, following CUMS exposure. Taken together, our study indicates that ketamine therapy can improve sensorimotor deficits co-morbid with a depressive disorder in parallel with modulation of the inflammatory system.

Combined Exposure to Chronic Sleep Deprivation and Caffeine Potentiates Behavioural Deficits by Altering Neurochemical Profile and Synaptophysin Expression in Long-Evans Rats.

Using the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm we developed, the combined effects of chronic sleep deprivation and high caffeine intake on prefrontal cortical synaptophysin expression, neurochemical profiles, and behavioural outcomes in Long-Evans rats were evaluated. The combination of chronic sleep deprivation and high-dose caffeine treatment produced varying degrees of behavioural impairments, depletion of antioxidants, serotonin, and an upregulation of acetylcholinesterase (AChE) activity in the prefrontal cortex. An immunohistochemical assessment revealed a reduction in synaptophysin protein expression in the prefrontal cortex following exposure to high-dose caffeine and chronic sleep deprivation. Overall, our findings support the advocacy for adequate sleep for optimal mental performance as a high intake of caffeine to attenuate the effects of sleep deprivation that may alter the neurochemical profile and synaptic plasticity in the prefrontal cortex, significantly increasing the risk of neuropsychiatric/degenerative disorders.

Fermented maize slurry (Ogi) and its supernatant (Omidun) mitigate elevated intraocular pressure by modulating BDNF expression and glial plasticity in the retina-gut axis of glaucomatous rats.

OBJECTIVES: Growing interest has been reported on the health benefits of fermented foods, which includes cognition enhancement and inflammation attenuation. BDNF is a known protectant against retinal degeneration, however, therapies that target this neurotrophic factor has been limited. Therefore, we assessed the reaction of BDNF and glial cells in glaucomatous rats and their response to treatment with fermented maize products. METHODS: Thirty male adult rats were either injected via the episcleral vein with hypertonic saline to elevate intraocular pressure (IOP) or treated with fermented maize slurry (Ogi) or its supernatant (Omidun). Following sacrifice, the retina and duodenum were studied by immunohistochemical analysis using antibodies directed against GFAP, AIF-1 and BDNF. RESULTS: Hypertonic saline injection produced hypertrophy of the Müller cells and increased GFAP and AIF-1 expression in the retina and gut when compared to the control. Treatment with Ogi and Omidun produced varying degrees of reduction of gliosis, protection against hypertonic saline-induced retinal ganglion cell loss, and reduced intraocular pressure. BDNF expression was downregulated following the hypertonic saline assault, while Omidun and Ogi treatment abrogated its reduction following the hypertonic saline assault. CONCLUSIONS: Collectively, our findings suggest that acute elevation of IOP alters crosstalk between gut and retina with consequent aberrant activation of glial cells; and that probiotic bacteria like the lactic acid bacteria rich in fermented foods including Ogi and Omidun may offer neuroprotection to the ganglionic cells by attenuating the retinal glial reaction and improving BDNF activity.

Lactobacillus plantarum mitigates sexual-reproductive deficits by modulating insulin receptor expression in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice.

OBJECTIVES: Hyperinsulinemia increases the risk factor of diabetes and infertility at a manifold. Lactobacillus plantarum has several medical significances with limited reports. Hence, this study assessed the effect of L. plantarum on sexual-reproductive functions and distribution of insulin receptors in the hypothalamic-pituitary-testicular axis of hyperinsulinemic mice. METHODS: Forty male adult mice were divided into five groups as follows: control, high-fat diet (HFD) + streptozotocin (STZ), therapeutic, co-administration group type 1 (CO-AD) and probiotics. They were either simultaneously exposed to an HFD and L. plantarum treatment for 28 days with a dose of STZ injection to induce hyperinsulinemia on day 28 or treated with L. plantarum for 14 days, and following induction of hyperinsulinemia. Mice were subjected to a sexual behavioural test and thereafter sacrificed under euthanasia condition. Blood, brain and testes were collected for biochemical and immunohistochemical assays. RESULTS: Treatment with L. plantarum ameliorated reproductive hormones activity disruption, sexual behavioural defects, antioxidant imbalance, insulin dysregulation and lipid metabolism dysfunction following exposure to HFD + STZ when compared to the hyperinsulinemic untreated mice. CONCLUSIONS: Taken together, data from this study reveal that L. plantarum abrogated hyperinsulinemia-induced male sexual and reproductive deficits by modulating antioxidant status, lipid metabolism and insulin signalling in the hypothalamic-pituitary-testicular axis of mice.

Virgin coconut oil abrogates depression-associated cognitive deficits by modulating hippocampal antioxidant balance, GABAergic and glutamatergic receptors in mice.

OBJECTIVES: GABA and glutamate neurotransmission play critical roles in both the neurobiology of depression and cognition; and Virgin coconut oil (VCO) is reported to support brain health. The present study investigated the effect of VCO on depression-associated cognitive deficits in mice. METHODS: Thirty male mice divided into five groups were either exposed to chronic unpredicted mild stress (CUMS) protocol for 28 days or pre-treated with 3 mL/kg b. wt. of VCO for 21 days or post-treated with 3 mL/kg b. wt. of VCO for 21 days following 28 days of CUMS exposure. Mice were subjected to behavioural assessments for depressive-like behaviours and short-term memory, and thereafter euthanised. Hippocampal tissue was dissected from the harvested whole brain for biochemical and immunohistochemical evaluations. RESULTS: Our results showed that CUMS exposure produced depressive-like behaviours, cognitive deficits and altered hippocampal redox balance. However, treatment with VCO abrogated depression-associated cognitive impairment, and enhanced hippocampal antioxidant concentration. Furthermore, immunohistochemical evaluation revealed significant improvement in GABAA and mGluR1a immunoreactivity following treatment with VCO in the depressed mice. CONCLUSIONS: Therefore, findings from this study support the dietary application of VCO to enhance neural resilience in patients with depression and related disorders.