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01-03-2020 | Alzheimer's Disease | Original Article

Verapamil attenuates scopolamine induced cognitive deficits by averting oxidative stress and mitochondrial injury – A potential therapeutic agent for Alzheimer’s Disease

Authors: Saravanaraman Ponne, Chinnadurai Raj Kumar, Rathanam Boopathy

Published in: Metabolic Brain Disease | Issue 3/2020

Abstract

Alzheimer’s disease (AD) is a multifactorial disorder where amyloid beta (Aβ) plaques, Ca²⁺ dysregulation, excessive oxidative stress, mitochondrial dysfunction and synaptic loss operate synergistically to bring about cholinergic deficits and dementia. New therapeutic interventions are gaining prominence as the morbidity and mortality of AD increases exponentially every year. Treating AD with antihypertensive drugs is thought to be a promising intervention; however, its mechanism of action of ameliorating AD needs further investigation. In this context, the present study explores the protective effect of verapamil, an antihypertensive agent of Ca²⁺ channel blocker (CCB) class against scopolamine-induced in vitro neurotoxicity and in vivo cognitive impairment. Supplementation of verapamil was found to attenuate oxidative stress by preventing mitochondrial injury, and augment the expression of genes involved in the cholinergic function (mACR1), synaptic plasticity (GAP43, SYP) and Ca²⁺-dependent memory-related genes (CREB1, CREBBP, BDNF). Further, verapamil treatment in mice attenuated the cognitive and behavioural deficits induced by scopolamine as measured by the elevated plus maze and passive avoidance test (P < 0.05). Thus, the present study demonstrates the neuroprotective effect of verapamil against the pathogenesis of AD such as oxidative stress, mitochondrial dysfunction and cognitive decline. These observations emphasize the importance of ‛Ca²⁺ dysregulation’ and ‛mitochondrial dysfunction’ theories in AD and recommends the supplementation of compounds that regulate Ca²⁺ homeostasis and mitochondrial function in susceptible AD individuals.

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Title: Verapamil attenuates scopolamine induced cognitive deficits by averting oxidative stress and mitochondrial injury – A potential therapeutic agent for Alzheimer’s Disease
Authors: Saravanaraman Ponne
Chinnadurai Raj Kumar
Rathanam Boopathy
Publication date: 01-03-2020
Publisher: Springer US
Keywords: Alzheimer's Disease
Verapamil
Alzheimer's Disease
Published in: Metabolic Brain Disease / Issue 3/2020
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-019-00498-x

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Verapamil attenuates scopolamine induced cognitive deficits by averting oxidative stress and mitochondrial injury – A potential therapeutic agent for Alzheimer’s Disease

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