中国病理生理杂志2025，Vol.41Issue(12)：2289-2298,10.DOI:10.3969/j.issn.1000-4718.2025.12.001
毛喉素通过激活cAMP/Epac信号通路改善敲除浦肯野细胞Celsr3后小鼠共济失调行为
Forskolin ameliorates ataxia-like behavior in Purkinje cell-Celsr3 cKO mice via cAMP/Epac signaling pathway
摘要
Abstract
AIM:To evaluate the function and mechanisms of forskolin in treating ataxia-like behavior in Celsr3 conditional knockout(cKO)mice.METHODS:The efficiency of intraperitoneally administered forskolin was evaluated by behavioral tests,and the molecular mechanisms were investigated by patch-clamp experiments.RESULTS:The loss of Celsr3 led to ataxia-like behavior,accompanied by impaired miniature excitatory postsynaptic currents(mEP-SCs)and postsynaptic long-term potentiation(LTP)in PCs.The cAMP activator forskolin ameliorated ataxia-like behav-ior and abrogated the mEPSCs impairment and LTP in model mice.Interestingly,the effects of forskolin could be blocked by SQ22536(a cAMP antagonist)and ESI-08(exchange protein activated by cAMP antagonist;Epac)but the H89(a PKA antagonist)could not block the effects.CONCLUSION:Celsr3 plays an important role in motor coordination by modulating synaptic function,and forskolin may be a valuable therapeutic drug for certain types of inherited cerebellar ataxia.关键词
毛喉素/共济失调/浦肯野细胞/Celsr3基因/cAMP/Epac信号通路Key words
forskolin/ataxia/Purkinje cells/Celsr3 gene/cAMP/Epac signaling pathway分类
医药卫生引用本文复制引用
吴楚粤,郭靖,洪途,黄羽,陈胜利,周芩稷..毛喉素通过激活cAMP/Epac信号通路改善敲除浦肯野细胞Celsr3后小鼠共济失调行为[J].中国病理生理杂志,2025,41(12):2289-2298,10.基金项目
Supported by the Natural Science Foundation of Chongqing Municipality,China(No.CSTB2022NSCQ-BHX0725)and the National Natural Science Foundation of China(No.82401728). （No.CSTB2022NSCQ-BHX0725）
