TY - JOUR
T1 - Persistent impact of amitriptyline on the behavior, brain neurotransmitter, and transcriptional profile of zebrafish (Danio rerio)
AU - Qiu, Xuchun
AU - Chen, Chen
AU - Shi, Yanhong
AU - Chen, Kun
AU - Li, Ming
AU - Xu, Hai
AU - Wu, Xiangyang
AU - Takai, Yuki
AU - Shimasaki, Yohei
AU - Oshima, Yuji
N1 - Funding Information:
This work was sponsored by the National Natural Science Foundation of China (Grant No. 32071623 ); the Natural Science Foundation of Jiangsu Province of China (Grant No. BK20191433 ); and Jiangsu Collaborative Innovation Center of Technology and Material of Water Treatment, Suzhou University of Science and Technology Suzhou 215009 , China.
Publisher Copyright:
© 2022
PY - 2022/4
Y1 - 2022/4
N2 - Discontinuation of amitriptyline (AMI) has been demonstrated to induce long-term withdrawal syndromes in mammals. However, no studies have focused on the persistent impacts of short-term AMI exposure on teleosts. Here, following exposure to AMI (2.5 and 40 μg/L) for 7 days (E7), zebrafish were transferred into AMI-free water to recover for 21 days (R21). The behavior, brain neurotransmitters, and brain transcriptional profiles were investigated on E7 and R21. AMI exposure induced persistent hypoactivity (2.5 and 40 μg/L) and abnormal schooling behavior (40 μg/L). AMI also induced long-term impacts on the brain serotonin (5-HT), 5-hydroxyindoleacetic acid, norepinephrine, and acetylcholine levels, several of which showed significant correlations with the locomotor activity or schooling behavior. Transcriptional analysis revealed persistent dysregulation in the pathways involved in the circadian rhythm, glycan biosynthesis and metabolism, and axon guidance in brain samples. Twelve genes were predicted as key driver genes in response to AMI exposure, and their significantly differential expression may direct changes across the related molecular networks. Moreover, upregulated brain 5-HT may serve as the central modulator of the persistent AMI pathogenesis in zebrafish. Considering AMI residues in natural waters may temporarily exceed μg/L, corresponding persistent adverse effects on teleosts should not be ignored.
AB - Discontinuation of amitriptyline (AMI) has been demonstrated to induce long-term withdrawal syndromes in mammals. However, no studies have focused on the persistent impacts of short-term AMI exposure on teleosts. Here, following exposure to AMI (2.5 and 40 μg/L) for 7 days (E7), zebrafish were transferred into AMI-free water to recover for 21 days (R21). The behavior, brain neurotransmitters, and brain transcriptional profiles were investigated on E7 and R21. AMI exposure induced persistent hypoactivity (2.5 and 40 μg/L) and abnormal schooling behavior (40 μg/L). AMI also induced long-term impacts on the brain serotonin (5-HT), 5-hydroxyindoleacetic acid, norepinephrine, and acetylcholine levels, several of which showed significant correlations with the locomotor activity or schooling behavior. Transcriptional analysis revealed persistent dysregulation in the pathways involved in the circadian rhythm, glycan biosynthesis and metabolism, and axon guidance in brain samples. Twelve genes were predicted as key driver genes in response to AMI exposure, and their significantly differential expression may direct changes across the related molecular networks. Moreover, upregulated brain 5-HT may serve as the central modulator of the persistent AMI pathogenesis in zebrafish. Considering AMI residues in natural waters may temporarily exceed μg/L, corresponding persistent adverse effects on teleosts should not be ignored.
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U2 - 10.1016/j.aquatox.2022.106129
DO - 10.1016/j.aquatox.2022.106129
M3 - Article
C2 - 35248893
AN - SCOPUS:85126823951
SN - 0166-445X
VL - 245
JO - Aquatic Toxicology
JF - Aquatic Toxicology
M1 - 106129
ER -