Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish.

Sreeja Sarasamma,Bonifasius Sampurna,Chung-Der Hsiao,Yu-Heng Lai,Stevhen Juniardi,Gilbert Audira,Sung-Tzu Liang,Erwei Hao

doi:10.3390/ijms19103195

Sreeja Sarasamma, Bonifasius Sampurna + Show 6 more

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https://doi.org/10.3390/ijms19103195

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Abstract

In this study, we evaluated the acute (24, 48, 72, and 96 h) and chronic (21 days) adverse effects induced by low doses (0.1, 0.5, 1, and 1.5 mg/L) of zinc chloride (ZnCl2) exposure in adult zebrafish by using behavioral endpoints like three-dimensional (3D) locomotion, passive avoidance, aggression, circadian rhythm, and predator avoidance tests. Also, brain tissues were dissected and subjected to analysis of multiple parameters related to oxidative stress, antioxidant responses, superoxide dismutase (SOD), neurotoxicity, and neurotransmitters. The results showed that ZnCl2-exposed fishes displayed decreased locomotor behavior and impaired short-term memory, which caused an Alzheimer’s Disease (AD)-like syndrome. In addition, low concentrations of ZnCl2 induced amyloid beta (amyloid β) and phosphorylated Tau (p-Tau) protein levels in brains. In addition, significant induction in oxidative stress indices (reactive oxygen species (ROS) and malondialdehyde (MDA)), reduction in antioxidant defense system (glutathione (GSH), GSH peroxidase (GSH-Px) and SOD) and changes in neurotransmitters were observed at low concentrations of ZnCl2. Neurotoxic effects of ZnCl2 were observed with significant inhibition of acetylcholine (ACh) activity when the exposure dose was higher than 1 ppm. Furthermore, we found that zinc, metallothionein (MT), and cortisol levels in brain were elevated compared to the control group. A significantly negative correlation was observed between memory and acetylcholinesterase (AChE) activity. In summary, these findings revealed that exposure to ZnCl2 affected the behavior profile of zebrafish, and induced neurotoxicity which may be associated with damaged brain areas related to memory. Moreover, our ZnCl2-induced zebrafish model may have potential for AD-associated research in the future.

Highlights

There are more than 50 million people living with Alzheimer’s Disease (AD) in the world; this is greater than the total population of Spain and is projected to reach nearly 150 million by 2050 [1]
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Zinc is widely considered as an essential trace element that is important for human health

Summary

Introduction

There are more than 50 million people living with Alzheimer’s Disease (AD) in the world; this is greater than the total population of Spain and is projected to reach nearly 150 million by 2050 [1]. It was hypothesized that the pathogenesis of AD is diverse, including free-radical-mediated processes [2], dysregulated membrane metabolism [3], trace element neurotoxicity [4], or combinations of the abovementioned factors. Another study suggested that the pyruvate transporter on the inner mitochondrial membrane impacts oxidative stress and lipid metabolism, playing a significant role in the pathogenesis of AD [5]. Among these factors, one which gained significant attention is the involvement of trace elements that caused toxicity during AD progression. Previous studies showed that imbalances of trace elements in homeostasis, such as bulk copper [6], bulk iron [7], and zinc [8,9,10], played an important role in the formation of senile plaques in the brain

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