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Developmental neurotoxicity of reserpine exposure in zebrafish larvae (Danio rerio).

Abstract

Reserpine is widely used for treatment of hypertension and schizophrenia. As a specific inhibitor of monoamine transporters, reserpine is known to deplete monoamine neurotransmitters and cause decreased movement symptoms. However, how zebrafish larvae respond to reserpine treatment is not well studied. Here we show that swimming distance and average velocity are significantly reduced after reserpine exposure under various stimulatory conditions. Using liquid chromatograph-mass spectrometer analysis, decreased levels of monoamines (e.g. dopamine, noradrenaline, and serotonin) were detected in reserpine-treated larvae. Moreover, reserpine treatment significantly reduced the number of dopaminergic neurons, which was identified with th (Tyrosine Hydroxylase) in situ hybridization in the preoptic area. Interestingly, dopaminergic neuron development-associated genes, such as otpa, otpb, wnt1, wnt3, wnt5 and manf, were downregulated in reserpine treated larvae. Our data indicates that 2 mg/L reserpine exposure induces dopaminergic neuron damage in the brain, demonstrating a chemical induced depression-like model in zebrafish larvae for future drug development.

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  • Authors+Show Affiliations

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    The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China; School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China.

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    State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan 430072, Hubei, PR China.

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    The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China; School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China.

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    The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China; School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China.

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    The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China; School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China.

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    The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China.

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    The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China; School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China.

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    School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China; School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China.

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    School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China.

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    Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, PR China; The Key Laboratory of Mental Disorder Management in Zhejiang Province, Hangzhou 310003, Zhejiang Province, PR China.

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    Yangtze Valley Water Environment Monitoring Center, Add: No.13, Yongqing Branch Road, Wuhan 430010, Hubei Province, PR China.

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    The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China; School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China. Electronic address: daikezhi@wmu.edu.cn.

    The Affiliated Kangning Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, PR China; School of Mental Health, Wenzhou Medical University, Wenzhou 32500, Zhejiang Province, PR China. Electronic address: xili_ihb@126.com.

    Source

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    31128281

    Citation

    Wang, Shao, et al. "Developmental Neurotoxicity of Reserpine Exposure in Zebrafish Larvae (Danio Rerio)." Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, vol. 223, 2019, pp. 115-123.
    Wang S, Duan M, Guan K, et al. Developmental neurotoxicity of reserpine exposure in zebrafish larvae (Danio rerio). Comp Biochem Physiol C Toxicol Pharmacol. 2019;223:115-123.
    Wang, S., Duan, M., Guan, K., Zhou, X., Zheng, M., Shi, X., ... Li, X. (2019). Developmental neurotoxicity of reserpine exposure in zebrafish larvae (Danio rerio). Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP, 223, pp. 115-123. doi:10.1016/j.cbpc.2019.05.008.
    Wang S, et al. Developmental Neurotoxicity of Reserpine Exposure in Zebrafish Larvae (Danio Rerio). Comp Biochem Physiol C Toxicol Pharmacol. 2019;223:115-123. PubMed PMID: 31128281.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Developmental neurotoxicity of reserpine exposure in zebrafish larvae (Danio rerio). AU - Wang,Shao, AU - Duan,Ming, AU - Guan,Kaiyu, AU - Zhou,Xianyong, AU - Zheng,Miaomiao, AU - Shi,Xulai, AU - Ye,Minjie, AU - Guan,Wanchun, AU - Kuver,Aarti, AU - Huang,Manli, AU - Liu,Yunbing, AU - Dai,Kezhi, AU - Li,Xi, Y1 - 2019/05/22/ PY - 2019/01/11/received PY - 2019/04/22/revised PY - 2019/05/10/accepted PY - 2019/5/28/pubmed PY - 2019/5/28/medline PY - 2019/5/26/entrez KW - Dopaminergic system KW - Reserpine KW - Zebrafish larvae SP - 115 EP - 123 JF - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP JO - Comp. Biochem. Physiol. C Toxicol. Pharmacol. VL - 223 N2 - Reserpine is widely used for treatment of hypertension and schizophrenia. As a specific inhibitor of monoamine transporters, reserpine is known to deplete monoamine neurotransmitters and cause decreased movement symptoms. However, how zebrafish larvae respond to reserpine treatment is not well studied. Here we show that swimming distance and average velocity are significantly reduced after reserpine exposure under various stimulatory conditions. Using liquid chromatograph-mass spectrometer analysis, decreased levels of monoamines (e.g. dopamine, noradrenaline, and serotonin) were detected in reserpine-treated larvae. Moreover, reserpine treatment significantly reduced the number of dopaminergic neurons, which was identified with th (Tyrosine Hydroxylase) in situ hybridization in the preoptic area. Interestingly, dopaminergic neuron development-associated genes, such as otpa, otpb, wnt1, wnt3, wnt5 and manf, were downregulated in reserpine treated larvae. Our data indicates that 2 mg/L reserpine exposure induces dopaminergic neuron damage in the brain, demonstrating a chemical induced depression-like model in zebrafish larvae for future drug development. SN - 1532-0456 UR - https://www.unboundmedicine.com/medline/citation/31128281/Developmental_neurotoxicity_of_reserpine_exposure_in_zebrafish_larvae_(Danio_rerio) L2 - https://linkinghub.elsevier.com/retrieve/pii/S1532-0456(19)30012-2 DB - PRIME DP - Unbound Medicine ER -