Reversal of behavioral decline and neuropathology by a complex vitamin supplement involves modulation of key neurochemical stressors

Olajide, Olayemi Joseph; Fatoye, John Oluwasegun; Idowu, Oluwakunmi Folashade; Ilekoya, Damilola; Gbadamosi, Ismail Temitayo; Gbadamosi, Monsurat Titi; Asogwa, Nnaemeka

doi:10.1016/j.etap.2018.07.005

Cited by 9 publications

(9 citation statements)

References 52 publications

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“…However, a high frequency of this behaviour shows a high level of anxiety (Holly et al, 2016). In line with findings from this study, aluminium has been reported to induce anxiety and memory decline (Crépeaux et al, 2017;Morris et al, 2017;Olajide et al, 2018). The anxiogenic propensity of aluminium can be attributed to the role it plays in mediating neurochemical disturbances and perturbation of neurotransmission in the brain (Caito and Aschner, 2015;Maya et al, 2016;Olajide et al, 2017a;Yokel, 2000).…”

Section: Discussionsupporting

confidence: 75%

Corticohippocampal Neuroenergetics and histomorphology in aluminium-induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine

Gbadamosi

Omotoso

2020

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Alzheimer's disease is the most common cause of dementia and is hallmarked by β-amyloid plaque and neurofibrillary tangles deposition in the CNS. The complex mechanism that underlies AD pathogenesis has made the development of a definitive cure futile. Exploring the possible therapeutic advantages of combining two neuromodulatory molecules with different mechanisms of neuroprotection is an interesting way of drug discovery. Ascorbic acid (AA), a potent antioxidant molecule, and nicotine (NIC), an allosteric modulator of nAChRs, have both been documented to independently proffer neuroprotection in experimental and clinical neurodegenerative cases. This study elucidated the putative therapeutic advantages of combining ascorbic acid and nicotine as a treatment regimen against the aluminium induced anxiety, corticohippocampal histopathology and perturbed neuroenergetics in rats induced with Alzheimer-like neuropathology Rats treated with 100 mg/kg aluminium chloride for 28 days presented with significantly increased stretch attend posture frequency and centre square entry. Aluminium significantly depleted the activities of G6PDH while increasing lactate levels. Corticohippocampal histomorphology of these animals showed poor histoarchitecture, increased congophilic and argentophilic densities that were coupled with increased anti-NSE immunopositivity. Animals post-treated with NIC (10mg/kg) and AA (100mg/kg) for 28 days presented with reduced anxiety level and improved corticohippocampal histomorphology. AA normalized G6PDH and lactate levels while the congophilic density was reduced by NIC. Corticohippocampal argentophilic density anti-NSE immunopositivity were also normalized by AA+NIC. The findings from this study have shown that a combination of ascorbic acid and nicotine effectively mitigated aluminium-induced corticohippocampal neuropathology and perturbed neuroenergetics.

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Section: Discussionsupporting

confidence: 75%

Corticohippocampal Neuroenergetics and histomorphology in aluminium-induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine

Gbadamosi

Omotoso

2020

Preprint

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“…A link between glutamate-mediated neurotoxicity and ROS overproduction was first proposed by the study of Dykens et al (1987), which observed that neuronal death caused by the excitotoxin kainite can be prevented by both superoxide dismutase through removal of superoxide anion (O 2− ) and by mannitol. Instructively, a lot of studies including ours have since shown that pathogenic mechanisms of AD also involve free radical accumulation and oxidative stress (Ding et al 2007;Swerdlow 2007;Saxena 2012;Ogundele et al 2014;Sanabria-Castro et al 2017;Olajide et al 2018). The roles of oxidative stress in glutamate evoked neurodegeneration in the present study are spotlighted by the depletion of GST and GPx enzymes in hippocampal lysates, which suggests increased expenditure of the endogenous antioxidant enzymes for housekeeping functions following abnormally elevated cytotoxic ROS molecules.…”

Section: Discussionmentioning

confidence: 50%

“…The Y-maze test was used to examine spatial working memory in this study as described previously (Olajide et al 2017(Olajide et al , 2018. Briefly, the procedure was performed in the Y-maze apparatus with 3 arms (Fig.…”

Section: Assessment Of Rats In the Y-mazementioning

confidence: 99%

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

et al. 2021

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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-β (Aβ) accumulation and increased glutamate agonist. While previous studies have shown Aβ-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, glutamatemediated 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.

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“…Reports of decreased exploratory and locomotor activities have been reported following AlCl 3 treatment. Our lab and others from literature have reported decreased crossing scores and altered secondary parameters such as rearing, grooming, and sniffing in the OFT following AlCl 3 treatment [ 25 , 26 ]. Decreased locomotor activity assessed by actophotometer following treatment with AlCl 3 was reported, and it was deduced from this study that this effect might be due to possible depressant effects of AlCl 3 on the CNS [ 23 ].…”

Section: Discussionmentioning

confidence: 97%

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

et al. 2020

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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 (AlCl 3)-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-AlCl 3 (100 mg/kg daily for 15 days); D-AlCl 3 then ESO (100 mg/kg AlCl 3 daily for 15 days followed by 50 mg/kg ESO daily for subsequent 15 days); E-ESO then AlCl 3 (50 mg/kg ESO daily for 15 days followed by 100 mg/kg AlCl 3 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 AlCl 3 toxicity, indicating its anxiolytic potentials. Additionally, AlCl 3 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 AlCl 3 toxicity.

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Reversal of behavioral decline and neuropathology by a complex vitamin supplement involves modulation of key neurochemical stressors

Cited by 9 publications

References 52 publications

Corticohippocampal Neuroenergetics and histomorphology in aluminium-induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine

Corticohippocampal Neuroenergetics and histomorphology in aluminium-induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine

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

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

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