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bioRxiv · 10.1101/2020.07.09.195495

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

Ismail Gbadamosi·Gabriel Omotoso
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Abstract

Alzheimers disease (AD) is the most common cause of dementia and is hallmarked by {beta}-amyloid plaque and neurofibrillary tangles deposition in the central nervous system. 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 Alzheimer-like corticohippocampal histopathology, anxiety, and perturbed neuroenergetics in rats induced with 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 glucose-6-phosphate dehydrogenase (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 histopathology and perturbed neuroenergetics.

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Ismail Gbadamosi, Gabriel Omotoso. 2020-07-10. Corticohippocampal Neuroenergetics and histomorphology in aluminium induced neurotoxicity: Putative therapeutic roles of ascorbic acid and nicotine. https://doi.org/10.1101/2020.07.09.195495

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