Anxiolytic, Promnesic, Anti-Acetylcholinesterase and Antioxidant Effects of Cotinine and 6-Hydroxy-L-Nicotine in Scopolamine-Induced Zebrafish (Danio rerio) Model of Alzheimer's Disease.

Razvan Stefan Boiangiu,Dragos Lucian Gorgan,Marius Mihasan,Lucian Hritcu,Bogdan Alexandru Stache

doi:10.3390/antiox10020212

Razvan Stefan Boiangiu, Dragos Lucian Gorgan + Show 3 more

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https://doi.org/10.3390/antiox10020212

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Journal: Antioxidants	Publication Date: Feb 1, 2021
Citations: 23	License type: CC BY 4.0

Affiliation: Alexandru Ioan Cuza University

Abstract

Cotinine (COT) and 6-hydroxy-L-nicotine (6HLN) are two nicotinic derivatives that possess cognitive-improving abilities and antioxidant properties in different rodent models of Alzheimer’s disease (AD), eluding the side-effects of nicotine (NIC), the parent molecule. In the current study, we evaluated the impact of COT and 6HLN on memory deterioration, anxiety, and oxidative stress in the scopolamine (SCOP)-induced zebrafish model of AD. For this, COT and 6HLN were acutely administered by immersion to zebrafish that were treated with SCOP before testing. The memory performances were assessed in Y-maze and object discrimination (NOR) tasks, while the anxiety-like behavior was evaluated in the novel tank diving test (NTT). The acetylcholinesterase (AChE) activity and oxidative stress were measured from brain samples. The RT-qPCR analysis was used to evaluate the npy, egr1, bdnf, and nrf2a gene expression. Our data indicated that both COT and 6HLN attenuated the SCOP-induced anxiety-like behavior and memory impairment and reduced the oxidative stress and AChE activity in the brain of zebrafish. Finally, RT-qPCR analysis indicated that COT and 6HLN increased the npy, egr1, bdnf, and nrf2a gene expression. Therefore, COT and 6HLN could be used as tools for improving AD conditions.

Highlights

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects over 50 million people worldwide, representing the most prevalent form of dementia and the fifth leading cause of death [1,2]
The cholinergic transmission is achieved through nicotinic acetylcholine receptors and muscarinic acetylcholine receptors, two families of ACh-binding receptors involved in cognitive processes and affected in AD [9]
The effects of COT and 6HLN acute treatment on anxiety-like behavior in zebrafish exposed to SCOP (100 μM) were assessed in novel tank diving test (NTT) by measuring the distance travelled and time spent by fish in the top zone of the tank

Summary

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects over 50 million people worldwide, representing the most prevalent form of dementia and the fifth leading cause of death [1,2]. AD neuropathology is characterized by intra- and extracellular accumulation of beta-amyloid (Aβ) peptide, the intracellular formation of neurofibrillary tangles (NFTs) of protein tau hyperphosphorylated, and the degeneration of cholinergic neurons accompanied by a reduction in acetylcholine (ACh) levels [5,6,7]. The cholinergic hypothesis of AD focuses on the degeneration of cholinergic neurons from the nucleus basalis of Meynert, which are involved in cognitive function, contributing to the memory loss exhibited by the AD patients [7,8]. The cholinergic transmission is achieved through nicotinic acetylcholine receptors (nAChRs) and muscarinic acetylcholine receptors (mAChRs), two families of ACh-binding receptors involved in cognitive processes and affected in AD [9].

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