Brain Disorders & Therapy

New prophylactic approach of combined therapy with memantine/donepezil and Leflunomide- for amyloid beta-induced Alzheimer's disease in rats

Global congress on Neuroscience Psychiatry and Mental disorder

July 03, 2023 | Webinar

Ahmad Bassiouny

Alexandria University, Egypt

Scientific Tracks Abstracts: Brain Disord Ther

Abstract:

Alzheimer's disease (AD) is the most common cause of dementia, accounting for approximately 60-70% of all cases. It is a progressive neurodegenerative disorder that primarily affects memory, thinking, and behavior. The pathophysiology of AD is characterized by the accumulation of senile plaques in brain tissue of betaamyloid plaques and neurofibrillary tangles derived from abnormal hyperphosphorylation of tau protein in the brain, leading to the loss of neurons and synaptic connections. In Alzheimer's disease (AD), the alterations primarily affect the hippocampus and cerebral cortex regions of the brain. Neuroinflammation refers to the brain's response to injury or pathological changes, characterized by the activation of glial cells, particularly astrocytes and microglia. Currently, there is no cure for Alzheimer's disease. The causes probably include a combination of age-related changes in the brain, along with genetic, environmental, and lifestyle factors, but it may be possible to hold off dementia. Our current objective is to investigate the effect of prophylactic combined therapy with memantine, a therapeutically used uncompetitive NMDA receptor antagonist, /donepezil in pre-treated rats with Leflunomide (Avara) in amyloid Beta-induced Alzheimer’s disease in rats. We use four groups (each of 10 rats): Group I: normal healthy rats receiving intracerebroventricular injection (icv) of citrate buffer solution. Group II: rats with induced AD by icv injection of 5 μl of Aβ25-35 solution (4 μg/μl) and receiving no treatment. Group III: Rats pre-treated with active form of Avara/day subcutaneously (s.c.) and administered memantine (5 mg/kg) 30 min before for two weeks with vitamin D supplement followed by induction of AD then post-treated with Avara in the same dose for 3 weeks. Group IV: rats with induced AD then post-treated with Avara for 3 weeks. The following parameters are evaluated in rats of all studied groups:1-Behavioral assessment: Morris water maze and open field tasks are performed post-icv injection for assessing cognitive, gross behavioral and motor activities of studied groups. 2-Biochemical tests: Hippocampal tissue levels of brain derived neurotrophic factor (BDNF), amyloid beta (Aβ) peptide, and antioxidant system; glutathione reductase (GR) and glutathione peroxidase (GPX). MicroRNAs have an eminent role in the pathogenesis of Alzheimer's Disease and will be monitored, especially for miR-132, miR-128 and miR-650 which influence AD pathogenesis through regulation of CDK5.This pretreatment regimen of these drugs could potentially provide enhanced anti-inflammatory effects, could potentially enhance, and protect the overall antioxidant defense in the brain. The concept behind combining leflunomide with memantine and donepezil with vitamin D supplementation is to target multiple mechanisms involved in AD pathogenesis. By addressing inflammation, glutamate toxicity, cholinergic deficits, and potential vitamin D deficiency, this approach aims to provide a comprehensive prophylactic strategy against AD. Further research, including well-designed clinical trials, is necessary to validate the efficacy, optimal dosages, and potential side effects of such a multi-targeted approach for AD prevention.

Biography :

Professor Ahmad R. Bassiouny is a renowned figure in the field of Molecular Therapeutics and Neuroscience. He currently holds the position of Professor of Molecular Therapeutics at Alexandria University, where he has been making significant contributions to the field for many years.Prof. Bassiouny's academic journey began with his appointment as an Assistant Professor at Alexandria University in 1985. Over the years, he steadily advanced in his career, becoming an Associate Professor in December 1995.