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

International Journal of Molecular Sciences

BonifasiusPutera Sampurna¹  Stevhen Juniardi¹  Sung-Tzu Liang¹  Yu-Heng Lai²  Gilbert Audira³  Chung-Der Hsiao³  Sreeja Sarasamma³  Erwei Hao⁴ 

[1] Department of Bioscience Technology, Chung Yuan Christian University, No. 200, Chung-Pei Rd., Chung-Li 32023, Taiwan;Department of Chemistry, Chinese Culture University, No. 55 Hwa-Kang Rd, Taipei 11114, Taiwan;Department of Chemistry, Chung Yuan Christian University, Chung-Li 32023, Taiwan;Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning 530200, Guangxi, China;

关键词: zebrafish;    AChE activity;    zinc chloride;    locomotor behavior;    p-Tau;    amyloid β;   

DOI  :  10.3390/ijms19103195

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown