Send Orders for Reprints to reprints@benthamscience.net CNS & Neurological Disorders - Drug Targets, XXXX, XX, XXX-XXX 1 RESEARCH ARTICLE 1871-5273/XX $65.00+.00 © XXXX Bentham Science Publishers Montelukast Ameliorates Scopolamine-induced Alzheimer’s Disease: Role on Cholinergic Neurotransmission, Antioxidant Defence System, Neuroinflammation and Expression of BDNF Bhavana Yerraguravagari 1 , Naga Pavani Penchikala 1 , Aravinda Sai Kolusu 1 , Grandhi Sandeep Ganesh 1 , Prasad Konduri 1 , Kumar V.S. Nemmani 1 and Pavan Kumar Samudrala 1,* 1 Department of Pharmacology, Shri Vishnu College of Pharmacy (SVCP) - Vishnupur, Bhimavaram - 534202, West Godavari, Andhra Pradesh, India Abstract: Background: Alzheimer's disease (AD) is an overwhelming neurodegenerative disease with progressive loss of memory. AD is characterized by the deposition of the senile plaques mainly composed of β-amyloid (Aβ) fragment, BDNF decline, Cholinergic system overactivity and neuroin- flammation. Montelukast (MTK), a leukotriene receptor antagonist, showed astounding neuroprotec- tive effects in a variety of neurodegenerative disorders. Objective: This study aims to investigate the ameliorative effects of Montelukast in the scopolamine- induced Alzheimer’s disease (AD) model in rats and evaluate its activity against neuroinflammation. Methods: Thirty rats were split into five groups: Control group (1 mL/kg normal saline, i.p.), Monte- lukast perse (10 mg/kg, i.p.), Disease group treated with Scopolamine (3 mg/kg, i.p.), Donepezil group (3 mg/kg, i.p.), Montelukast treatment group (10 mg/kg, i.p.) and behavioural and biochemical tests were carried out to assess the neuro protective effect. Results: Scopolamine treatment led to a significant reduction in learning and memory and an eleva- tion in cholinesterase levels when compared with the control group (p < 0.01). Additionally, elevated oxidative stress and Amyloid-β levels were associated with enhanced neuroinflammation (p < 0.05, p < 0.01). Furthermore, the decline in neurotrophic factor BDNF is also observed when compared with the normal control group (p < 0.01). Montelukast pre-treatment significantly attenuated learning and memory impairment and cholinesterase levels. Besides, Montelukast and standard drug donepezil administration significantly suppressed the oxidative stress markers (p < 0.01), Amyloid-β levels, neuroinflammatory mediators (p < 0.05) and caused a significant increase in BDNF levels (p < 0.05) Conclusion: Montelukast bestowed ameliorative effects in scopolamine-induced AD animal models as per the previous studies via attenuation of memory impairment, cholinesterase neurotransmission, oxidative stress, Amyloid-β levels, neuroinflammatory mediators and enhanced BDNF levels. A R T I C L E H I S T O R Y Received: April 17, 2023 Revised: July 20, 2023 Accepted: July 24, 2023 DOI: 10.2174/0118715273258337230925040049 Keywords: Cognitive impairment, scopolamine, montelukast, BDNF expression, oxidative stress, neuroinflammation. 1. INTRODUCTION Alzheimer’s disease (AD) is a multifactorial, irreversible and progressive neurodegenerative disorder characterized by Amyloid-β (Aβ) deposition in neocortical terminal fields and neurofibrillary tangles in medial temporal lobes [1, 2]. AD is an age-related disease that mainly affects 10 individ- uals per 1,00,000 population every year [3]. According to *Address correspondence to this author at the Department of Pharmacolo- gy, Shri Vishnu College of Pharmacy, Bhimavaram, West Godavari, 534202, India; Tel: +91-8876430896; E-mails: pavanniper199@gmail.com; pavankumar.s@svcp.edu.in The Lancet Public Health, the number of people living with AD will exceed 152 million cases globally by 2050 [4]. The neuropathological hallmark features of AD are Aβ plaque deposition and hyperphosphorylated tau proteins accompa- nied by amyloid angiopathy, impaired neurogenesis, cholin- ergic dysfunction, oxidative stress and neuroinflammation [5-7]. Cortical and hippocampal regions of the brain engaged in cognitive functions like learning and memory require cholinergic innervation [8]. Any abnormal changes in cho- linergic neurotransmission promote Amyloid-β (Aβ) deposi- tion through alterations and changes in amyloid precursor