| Literature DB >> 33608505 |
Moran Guo1,2, Can Cui1, Xueqin Song1,2, Lijing Jia1,2, Duan Li1, Xiuli Wang1, Hui Dong1,2, Yanqin Ma3, Yaling Liu1,2, Zhiqiang Cui4, Le Yi1,2, Zhongyao Li1,2, Yue Bi1,2, Yuanyuan Li1,2, Yakun Liu1,2, Weisong Duan5,6, Chunyan Li7,8.
Abstract
Fibroblast growth factor 9 (FGF9) has long been assumed to modulate multiple biological processes, yet very little is known about the impact of FGF9 on neurodevelopment. Herein, we found that loss of Fgf9 in olig1 progenitor cells induced epilepsy in mice, with pathological changes in the cortex. Then depleting Fgf9 in different neural populations revealed that epilepsy was associated with GABAergic neurons. Fgf9 CKO in GABAergic neuron (CKOVGAT) mice exhibited not only the most severe seizures, but also the most severe growth retardation and highest mortality. Fgf9 deletion in CKOVGAT mice caused neuronal apoptosis and decreased GABA expression, leading to a GABA/Glu imbalance and epilepsy. The adenylate cyclase/cyclic AMP and ERK signaling pathways were activated in this process. Recombinant FGF9 proteoliposomes could significantly decrease the number of seizures. Furthermore, the decrease of FGF9 was commonly observed in serum of epileptic patients, especially those with focal seizures. Thus, FGF9 plays essential roles in GABAergic neuron survival and epilepsy pathology, which could serve as a new target for the treatment of epilepsy.Entities:
Year: 2021 PMID： 33608505 PMCID： PMC7896082 DOI： 10.1038/s41419-021-03478-1
Source DB: PubMed Journal: Cell Death Dis Impact factor: 8.469