PUBLICATION
Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish
- Authors
- Sarasamma, S., Audira, G., Juniardi, S., Sampurna, B.P., Liang, S.T., Hao, E., Lai, Y.H., Hsiao, C.D.
- ID
- ZDB-PUB-181020-1
- Date
- 2018
- Source
- International Journal of Molecular Sciences 19(10): (Journal)
- Registered Authors
- Hsiao, Chung-Der
- Keywords
- AChE activity, amyloid β, locomotor behavior, p-Tau, zebrafish, zinc chloride
- MeSH Terms
-
- Acetylcholine/metabolism*
- Aggression
- Aging/physiology*
- Alzheimer Disease/pathology
- Animals
- Avoidance Learning
- Biomarkers/metabolism
- Brain/metabolism*
- Chlorides/adverse effects*
- Circadian Rhythm/radiation effects
- Down-Regulation/radiation effects
- Memory, Short-Term*/radiation effects
- Motor Activity*/radiation effects
- Neurotoxins/metabolism*
- Neurotransmitter Agents/metabolism
- Oxidative Stress/radiation effects
- Predatory Behavior
- Zebrafish/physiology*
- Zinc Compounds/adverse effects*
- PubMed
- 30332818 Full text @ Int. J. Mol. Sci.
Citation
Sarasamma, S., Audira, G., Juniardi, S., Sampurna, B.P., Liang, S.T., Hao, E., Lai, Y.H., Hsiao, C.D. (2018) Zinc Chloride Exposure Inhibits Brain Acetylcholine Levels, Produces Neurotoxic Signatures, and Diminishes Memory and Motor Activities in Adult Zebrafish. International Journal of Molecular Sciences. 19(10).
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping