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

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 (), Wenqing Zhang () and Zhibin Huang ()
Additional contact information
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
Juan Shen: Guangdong Pharmaceutical University
Wenqing Zhang: South China University of Technology
Zhibin Huang: South China University of Technology

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41114-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41114-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41114-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().