IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41114-y.html
   My bibliography  Save this article

Sulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish

Author

Listed:
  • Wenwei Sun

    (South China University of Technology)

  • Meimei Wang

    (South China University of Technology)

  • Jun Zhao

    (South China University of Technology)

  • Shuang Zhao

    (South China University of Technology)

  • Wenchao Zhu

    (South China University of Technology)

  • Xiaoting Wu

    (Guangdong Pharmaceutical University)

  • Feifei Li

    (South China University of Technology)

  • Wei Liu

    (South China University of Technology)

  • Zhuo Wang

    (South China University of Technology)

  • Meng Gao

    (South China University of Technology)

  • Yiyue Zhang

    (South China University of Technology)

  • Jin Xu

    (South China University of Technology)

  • Meijia Zhang

    (South China University of Technology)

  • Qiang Wang

    (South China University of Technology)

  • Zilong Wen

    (Clear Water Bay, Kowloon
    Shenzhen Peking University-Hong Kong University of Science and Technology Medical Center)

  • Juan Shen

    (Guangdong Pharmaceutical University)

  • Wenqing Zhang

    (South China University of Technology
    Shenzhen Bay Laboratory)

  • Zhibin Huang

    (South China University of Technology)

Abstract

Nonsteroidal anti-inflammatory drugs compose one of the most widely used classes of medications, but the risks for early development remain controversial, especially in the nervous system. Here, we utilized zebrafish larvae to assess the potentially toxic effects of nonsteroidal anti-inflammatory drugs and found that sulindac can selectively induce apoptosis of GABAergic neurons in the brains of zebrafish larvae brains. Zebrafish larvae exhibit hyperactive behaviour after sulindac exposure. We also found that akt1 is selectively expressed in GABAergic neurons and that SC97 (an Akt1 activator) and exogenous akt1 mRNA can reverse the apoptosis caused by sulindac. Further studies showed that sulindac binds to retinoid X receptor alpha (RXRα) and induces autophagy in GABAergic neurons, leading to activation of the mitochondrial apoptotic pathway. Finally, we verified that sulindac can lead to hyperactivity and selectively induce GABAergic neuron apoptosis in mice. These findings suggest that excessive use of sulindac may lead to early neurodevelopmental toxicity and increase the risk of hyperactivity, which could be associated with damage to GABAergic neurons.

Suggested Citation

  • Wenwei Sun & Meimei Wang & Jun Zhao & Shuang Zhao & Wenchao Zhu & Xiaoting Wu & Feifei Li & Wei Liu & Zhuo Wang & Meng Gao & Yiyue Zhang & Jin Xu & Meijia Zhang & Qiang Wang & Zilong Wen & Juan Shen &, 2023. "Sulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41114-y
    DOI: 10.1038/s41467-023-41114-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41114-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41114-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. J. Gray Camp & Keisuke Sekine & Tobias Gerber & Henry Loeffler-Wirth & Hans Binder & Malgorzata Gac & Sabina Kanton & Jorge Kageyama & Georg Damm & Daniel Seehofer & Lenka Belicova & Marc Bickle & Ric, 2017. "Multilineage communication regulates human liver bud development from pluripotency," Nature, Nature, vol. 546(7659), pages 533-538, June.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jing Qi & Yang Zhou & Zicen Zhao & Shuilin Jin, 2021. "SDImpute: A statistical block imputation method based on cell-level and gene-level information for dropouts in single-cell RNA-seq data," PLOS Computational Biology, Public Library of Science, vol. 17(6), pages 1-20, June.
    2. Maisumu Gulimiheranmu & Shuang Li & Junmei Zhou, 2021. "In Vitro Recapitulation of Neuropsychiatric Disorders with Pluripotent Stem Cells-Derived Brain Organoids," IJERPH, MDPI, vol. 18(23), pages 1-14, November.
    3. Chieh Lin & Jun Ding & Ziv Bar-Joseph, 2020. "Inferring TF activation order in time series scRNA-Seq studies," PLOS Computational Biology, Public Library of Science, vol. 16(2), pages 1-19, February.
    4. Peizhuo Wang & Xiao Wen & Han Li & Peng Lang & Shuya Li & Yipin Lei & Hantao Shu & Lin Gao & Dan Zhao & Jianyang Zeng, 2023. "Deciphering driver regulators of cell fate decisions from single-cell transcriptomics data with CEFCON," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41114-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.