Valorization of Therapeutics Potential of a TRPC1 Ion Channel Modulator in Scopolamine-induced Neurodegeneration in Rat

Abstract

Introduction Alzheimer's disease (AD) coincides with irreversible, worsening impairment of memory and β-amyloid (Aβ) deposition in brain. Aggregation of Aβ leads to neurological impairment. It has become imperative to investigate more treatments for AD due to the detrimental effects it has on both health and the economy. Currently approved drug by US FDA for treatment of AD includes NMDA antagonist Donepezil, Rivastigmine and Galantamine.2-APB is a novel molecule which show neuroprotective effect via modulating Ca2+channel. Aim and Objectives Aim of the research study is to investigate the therapeutic potential of 2-APB, a TRPC1 inhibitor in scopolamine-induced neurodegeneration in rats and to investigate potential role of 2-APB on cognitive changes, neurochemical and to elucidate possible mechanism of 2-APB. Methods Male and Female wistar rats were used and divided into six group (n=6) Control (Normal Saline), Diseases Control (Treated with scopolamine 2mg/kg i.p.), 2-APB (10mg/kg/day i.p.), 2-APB (5mg/kg/day i.p.), 2-APB (2.5mg/kg/day i.p.) and Diseases treated with Donepezil (5mg/kg/day o.p.) for 21 days from day 0 when scopolamine was administered. Results In neurobehavioral parameters, reduced escape latency time to locate the platform in Morris water Maze was observed treated with 2-APB. Biochemical estimation revealed, decreased levels of MDA, Total Protein and Catalase activity in treatment group and increased levels of GSH in animals treated with 2-APB compared to the disease control group. In Histopathological analysis reduction in neuronal cell loss and cell density was observed. Treatment with 2-APB, however, prevented this cognitive decline in the scopolamine-induced Alzheimer's disease model. These findings suggest that 2-APB may modulate cholinergic neurotransmission, the antioxidant system, and neuroinflammatory markers (TNF-α, IL-1β, IL-6) in the brain, thereby improving cognitive function.