Pamiparib Induces Neurodevelopmental Defects and Cerebral Haemorrhage in Zebrafish Embryos via Inhibiting Notch Signalling
Pamiparib Induces Neurodevelopmental Defects and Cerebral Haemorrhage in Zebrafish Embryos via Inhibiting Notch Signalling
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Pamiparib 通过抑制 Notch 信号诱导斑马鱼胚胎神经发育缺陷和脑出血
DOI：
10.1007/s12035-022-02988-z
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发表时间：
2022-08
影响因子：
5.1
通讯作者：
Zigang Cao
中科院分区：
文献类型：
--
作者：
Dou Yang;Fasheng Liu;Mengqi Wan;Jieping Liu;Ling Huang;Chao Chen;Xue Li;Li Zhang;Xiaobing Ding;Xinjun Liao;Guanghua Xiong;Huiqiang Lu;Juhua Xiao;Zigang Cao
Pamiparib是一种用于临床研究的聚adp核糖聚合酶（PARP）抑制剂，可有效穿透血脑屏障。目前，关于其对脊椎动物神经发育影响的研究很少。在本研究中，我们将斑马鱼胚胎在受精后6至72 h暴露于1、2和3µM的Pamiparib中。结果表明，帕米帕尼能特异性诱导鱼幼体脑出血、脑萎缩和运动障碍。此外，帕米帕尼暴露导致乙酰胆碱酯酶（AChE）和三磷酸腺苷酶（ATPase）活性下调，氧化应激上调，从而导致细胞凋亡，破坏参与神经发育、神经递质通路和帕金森病（PD）样症状的基因表达。同时，虾青素可以通过下调氧化应激来部分修复神经发育缺陷。暴露于帕米帕尼后，Notch信号下调，使用Notch信号激活剂可以部分挽救神经发育毒性。因此，我们的研究表明帕米帕利可能通过下调Notch信号通路诱导斑马鱼神经毒性，为帕米帕利在胚胎发育过程中潜在的神经毒性提供了参考。
Pamiparib is a poly ADP-ribose polymerase (PARP) inhibitor used in clinical studies, which can penetrate the blood–brain barrier efficiently. At present, there are few studies on its effect on vertebrate neurodevelopment. In this study, we exposed zebrafish embryos to 1, 2 and 3 µM of Pamiparib from 6 to 72 h post-fertilisation (hpf). Results showed that pamiparib can specifically induce cerebral haemorrhage, brain atrophy and movement disorders in fish larvae. In addition, pamiparib exposure leads to downregulation of acetylcholinesterase (AChE) and adenosine triphosphate (ATPase) activities, and upregulation of oxidative stress which then leads to apoptosis and disrupts the gene expression involved in the neurodevelopment, neurotransmitter pathways and Parkinson’s disease (PD) like symptoms. Meanwhile, astaxanthin can partially rescue neurodevelopmental defects by downregulating oxidative stress. After exposure to pamiparib, the Notch signalling is downregulated, and the use of an activator of Notch signalling can partially rescue neurodevelopmental toxicity. Therefore, our research indicates that pamiparib may induce zebrafish neurotoxicity by downregulating Notch signalling and provides a reference for the potential neurotoxicity of pamiparib during embryonic development.
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影响因子：
5.5
作者：
Song YS;Dai MZ;Zhu CX;Huang YF;Liu J;Zhang CD;Xie F;Peng Y;Zhang Y;Li CQ;Zhang LJ
通讯作者：
Zhang LJ
DOI：
10.1186/1478-811x-8-31
发表时间：
2010-12-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Chaitanya GV;Steven AJ;Babu PP
通讯作者：
Babu PP
DOI：
10.1101/346007
发表时间：
2018-06
期刊：
bioRxiv
影响因子：
--
作者：
Jingying Chen;Jianbo He;Qifen Yang;Yaoguang Zhang;L. Luo
通讯作者：
Jingying Chen;Jianbo He;Qifen Yang;Yaoguang Zhang;L. Luo
影响因子：
12.4
作者：
Farrés J;Llacuna L;Martin-Caballero J;Martínez C;Lozano JJ;Ampurdanés C;López-Contreras AJ;Florensa L;Navarro J;Ottina E;Dantzer F;Schreiber V;Villunger A;Fernández-Capetillo O;Yélamos J
通讯作者：
Yélamos J
影响因子：
20.3
作者：
Kannan, Sankaranarayanan;Fang, Wendy;Zweidler-McKay, Patrick A.
通讯作者：
Zweidler-McKay, Patrick A.