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Deletion of FGF9 in GABAergic neurons causes epilepsy

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. Th...

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Autores principales: Guo, Moran, Cui, Can, Song, Xueqin, Jia, Lijing, Li, Duan, Wang, Xiuli, Dong, Hui, Ma, Yanqin, Liu, Yaling, Cui, Zhiqiang, Yi, Le, Li, Zhongyao, Bi, Yue, Li, Yuanyuan, Liu, Yakun, Duan, Weisong, Li, Chunyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896082/
https://www.ncbi.nlm.nih.gov/pubmed/33608505
http://dx.doi.org/10.1038/s41419-021-03478-1
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author Guo, Moran
Cui, Can
Song, Xueqin
Jia, Lijing
Li, Duan
Wang, Xiuli
Dong, Hui
Ma, Yanqin
Liu, Yaling
Cui, Zhiqiang
Yi, Le
Li, Zhongyao
Bi, Yue
Li, Yuanyuan
Liu, Yakun
Duan, Weisong
Li, Chunyan
author_facet Guo, Moran
Cui, Can
Song, Xueqin
Jia, Lijing
Li, Duan
Wang, Xiuli
Dong, Hui
Ma, Yanqin
Liu, Yaling
Cui, Zhiqiang
Yi, Le
Li, Zhongyao
Bi, Yue
Li, Yuanyuan
Liu, Yakun
Duan, Weisong
Li, Chunyan
author_sort Guo, Moran
collection PubMed
description 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 (CKO(VGAT)) mice exhibited not only the most severe seizures, but also the most severe growth retardation and highest mortality. Fgf9 deletion in CKO(VGAT) 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.
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spelling pubmed-78960822021-03-03 Deletion of FGF9 in GABAergic neurons causes epilepsy Guo, Moran Cui, Can Song, Xueqin Jia, Lijing Li, Duan Wang, Xiuli Dong, Hui Ma, Yanqin Liu, Yaling Cui, Zhiqiang Yi, Le Li, Zhongyao Bi, Yue Li, Yuanyuan Liu, Yakun Duan, Weisong Li, Chunyan Cell Death Dis Article 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 (CKO(VGAT)) mice exhibited not only the most severe seizures, but also the most severe growth retardation and highest mortality. Fgf9 deletion in CKO(VGAT) 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. Nature Publishing Group UK 2021-02-19 /pmc/articles/PMC7896082/ /pubmed/33608505 http://dx.doi.org/10.1038/s41419-021-03478-1 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Guo, Moran
Cui, Can
Song, Xueqin
Jia, Lijing
Li, Duan
Wang, Xiuli
Dong, Hui
Ma, Yanqin
Liu, Yaling
Cui, Zhiqiang
Yi, Le
Li, Zhongyao
Bi, Yue
Li, Yuanyuan
Liu, Yakun
Duan, Weisong
Li, Chunyan
Deletion of FGF9 in GABAergic neurons causes epilepsy
title Deletion of FGF9 in GABAergic neurons causes epilepsy
title_full Deletion of FGF9 in GABAergic neurons causes epilepsy
title_fullStr Deletion of FGF9 in GABAergic neurons causes epilepsy
title_full_unstemmed Deletion of FGF9 in GABAergic neurons causes epilepsy
title_short Deletion of FGF9 in GABAergic neurons causes epilepsy
title_sort deletion of fgf9 in gabaergic neurons causes epilepsy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896082/
https://www.ncbi.nlm.nih.gov/pubmed/33608505
http://dx.doi.org/10.1038/s41419-021-03478-1
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