Vitamin D attenuates monosodium glutamate-induced behavioural anomalies, metabolic dysregulation, cholinergic impairment, oxidative stress, and astrogliosis in rats.

BACKGROUND: Monosodium glutamate (MSG) is a commonly used flavor enhancer that has raised concerns due to its potential adverse effects on various organs. This study explored the neuroprotective potential of Vitamin D, a beneficial micronutrient, in mitigating MSG-induced neurotoxicity. MATERIALS & METHODS: Adult male Wistar rats were categorized into five groups: control (2ml/kg PBS orally for 30 days), MSG (40mg/kg orally for 30 days), VIT-D (oral cholecalciferol; 500 IU/kg for 30 days), MSG+VIT-D (MSG for 30 days followed by VIT-D for another 30 days), and VIT-D/MSG (concurrent VIT-D and MSG for 30 days). The rats underwent neurobehavioral, histochemical, and biochemical analyses following the treatments. RESULTS: MSG treatment caused a decline in both long and short-term memory, along with reduced exploratory and anxiogenic behavior, mitigated by vitamin D treatment. MSG exposure also induced impaired behavior, dyslipidemia, oxidative stress, lipid peroxidation, altered cholinergic transmission, and increased chromatolysis and neuroinflammation in the frontal cortex, hippocampus, and cerebellum. CONCLUSIONS: VIT-D demonstrated a mitigating effect on MSG-induced adverse outcomes, highlighting its potential to attenuate neurodegenerative cascades. This investigation contributes to understanding MSG-associated neurotoxicity and suggests vitamin D as a valuable and potential intervention for neuroprotection.

Hippocampal Degeneration and Behavioral Impairment During Alzheimer-Like Pathogenesis Involves Glutamate Excitotoxicity.

The hallmarks of Alzheimer's disease (AD) pathology include senile plaques accumulation and neurofibrillary tangles, which is thought to underlie synaptic failure. Recent evidence however supports that synaptic failure in AD may instead be instigated by enhanced N-methyl-D-aspartate (NMDA) activity, via a reciprocal relationship between soluble amyloid-ß (Aß) accumulation and increased glutamate agonist. While previous studies have shown Aß-mediated alterations to the glutamatergic system during AD, the underlying etiology of excitotoxic glutamate-induced changes has not been explored. Here, we investigated the acute effects of stereotaxic dentate gyrus (DG) glutamate injection on behavior and molecular expression of specific proteins and neurochemicals modulating hippocampal functions. Dependence of glutamate-mediated effects on NMDA receptor (NMDAR) hyperactivation was tested using NMDARs antagonist memantine. DG of Wistar rats (12-weeks-old) were bilaterally microinjected with glutamate (500 mM) with or without daily intraperitoneal (i.p.) memantine injection (20 mg/kg) for 14 days, while controls received either intrahippocampal/i.p. PBS or i.p. memantine. Behavioral characterization in open field and Y-maze revealed that glutamate evoked anxiogenic responses and perturbed spatial memory were inhibited by memantine. In glutamate-treated rats, increased NO expression was accompanied by marked reduction in profiles of glutathione-s-transferase and glutathione peroxidase. Similarly, glutamate-mediated increase in acetylcholinesterase expression corroborated downregulation of synaptophysin and PSD-95, coupled with initiation of reactive astrogliosis (GFAP). While neurofilament immunolocalization/immunoexpression was unperturbed, we found glutamate-mediated reduction in neurogenic markers Ki67 and PCNA immunoexpression, with a decrease in NR2B protein expression, whereas mGluR1 remains unchanged. In addition, increased expression of apoptotic regulatory proteins p53 and Bax was seen in glutamate infused rats, corroborating chromatolytic degeneration of granule neurons in the DG. Interestingly, memantine abrogated most of the degenerative changes associated with glutamate excitotoxicity in this study. Taken together, our findings causally link acute glutamate dyshomeostasis in the DG with development of AD-related behavioral impairment and molecular neurodegeneration.

Inhibitory potentials of Cymbopogon citratus oil against aluminium-induced behavioral deficits and neuropathology in rats / 대한해부학회지

Cymbopogon citratus is a tropical phytomedicinal plant that is widely known for its hypoglycemic, hypolipidemic, anxiolytic, sedative, antioxidative and anti-inflammatory properties. In this study, we have examined the neuroprotective effects of the essential oil (ESO) of Cymbopogon citratus, following aluminum chloride (AlCl3)-induced neurotoxicity within the cerebellum of Wistar rats. A total of 40 adult male Wistar rats were assigned into five groups and treated orally as follows: A–phosphate-buffered saline (1 ml daily for 15 days); B–ESO (50 mg/kg daily for 15 days); C–AlCl3 (100 mg/kg daily for 15 days); D–AlCl3 then ESO (100 mg/kg AlCl3 daily for 15 days followed by 50 mg/kg ESO daily for subsequent 15 days); E– ESO then AlCl3 (50 mg/kg ESO daily for 15 days followed by 100 mg/kg AlCl3 daily for following 15 days). To address our questions, we observed the locomotion and exploratory behavior of the rats in the open field apparatus and subsequently evaluated cerebellar oxidative redox parameters, neural bioenergetics, acetylcholinesterase levels, transferrin receptor protein, and total protein profiles by biochemical assays. Furthermore, we investigated cerebellar histomorphology and Nissl profile by H&E and Cresyl violet Nissl staining procedures. ESO treatment markedly attenuated deficits in exploratory activities and rearing behavior following AlCl3 toxicity, indicating its anxiolytic potentials. Additionally, AlCl3 evokedincrease in malondialdehyde and nitric oxide levels, as well as repressed cerebellar catalase, glutathione peroxidase, and superoxide dismutase profiles were normalised to baseline levels by ESO treatment. Treatment with ESO, ergo, exhibits substantial neuroprotective and modulatory potentials in response to AlCl3 toxicity.

Inhibitory potentials of Cymbopogon citratus oil against aluminium-induced behavioral deficits and neuropathology in rats / 대한해부학회지

Cymbopogon citratus is a tropical phytomedicinal plant that is widely known for its hypoglycemic, hypolipidemic, anxiolytic, sedative, antioxidative and anti-inflammatory properties. In this study, we have examined the neuroprotective effects of the essential oil (ESO) of Cymbopogon citratus, following aluminum chloride (AlCl3)-induced neurotoxicity within the cerebellum of Wistar rats. A total of 40 adult male Wistar rats were assigned into five groups and treated orally as follows: A–phosphate-buffered saline (1 ml daily for 15 days); B–ESO (50 mg/kg daily for 15 days); C–AlCl3 (100 mg/kg daily for 15 days); D–AlCl3 then ESO (100 mg/kg AlCl3 daily for 15 days followed by 50 mg/kg ESO daily for subsequent 15 days); E– ESO then AlCl3 (50 mg/kg ESO daily for 15 days followed by 100 mg/kg AlCl3 daily for following 15 days). To address our questions, we observed the locomotion and exploratory behavior of the rats in the open field apparatus and subsequently evaluated cerebellar oxidative redox parameters, neural bioenergetics, acetylcholinesterase levels, transferrin receptor protein, and total protein profiles by biochemical assays. Furthermore, we investigated cerebellar histomorphology and Nissl profile by H&E and Cresyl violet Nissl staining procedures. ESO treatment markedly attenuated deficits in exploratory activities and rearing behavior following AlCl3 toxicity, indicating its anxiolytic potentials. Additionally, AlCl3 evokedincrease in malondialdehyde and nitric oxide levels, as well as repressed cerebellar catalase, glutathione peroxidase, and superoxide dismutase profiles were normalised to baseline levels by ESO treatment. Treatment with ESO, ergo, exhibits substantial neuroprotective and modulatory potentials in response to AlCl3 toxicity.

Ascorbic acid ameliorates behavioural deficits and neuropathological alterations in rat model of Alzheimer's disease.

Exploring the links between neural pathobiology and behavioural deficits in Alzheimer's disease (AD), and investigating substances with known therapeutic advantages over subcellular mechanisms underlying these dysfunctions could advance the development of potent therapeutic molecules for AD treatment. Here we investigated the efficacy of ascorbic acid (AA) in reversing aluminium chloride (AlCl3)-induced behavioural deficits and neurotoxic cascades within prefrontal cortex (PFC) and hippocampus of rats. A group of rats administered oral AlCl3 (100mg/kg) daily for 15days showed degenerative changes characterised by significant weight loss, reduced exploratory/working memory, frontal-dependent motor deficits, cognitive decline, memory dysfunction and anxiety during behavioural assessments compared to control. Subsequent analysis showed that oxidative impairment-indicated by depleted superoxide dismutase and lipid peroxidation (related to glutathione-S-transferase activity), cholinergic deficits seen by increased neural acetylcholinesterase (AChE) expression and elevated lactate dehydrogenase underlie behavioural alterations. Furthermore, evidences of proteolysis were seen by reduced Nissl profiles in neuronal axons and dendrites which correspond to apoptotic changes observed in H&E staining of PFC and hippocampal sections. Interestingly, AA (100mg/kg daily for 15days) significantly attenuated behavioural deficits in rats through inhibition of molecular and cellular stressor proteins activated by AlCl3. Our results showed that the primary mechanisms underlying AA therapeutic advantages relates closely with its abilities to scavenge free radicals, prevent membrane lipid peroxidation, modulate neuronal bioenergetics, act as AChE inhibitor and through its anti-proteolytic properties. These findings suggest that supplementing endogenous AA capacity through its pharmacological intake may inhibit progression of AD-related neurodegenerative processes and behavioural alterations.