Department of Neurosurgery, Xinqiao Hospital, Army Medical University, 183 Xinqiao Main Street, Shapingba District, Chongqing 400037, China.
Department of Pedatrics, Xinqiao Hospital, Army Medical University, 183 Xinqiao Main Street, Shapingba District, Chongqing 400037, China.
Cereb Cortex. 2022 Nov 21;32(23):5259-5272. doi: 10.1093/cercor/bhac012.
Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults, with pathological mechanisms remaining to be fully elucidated. Fibroblast Growth Factor 13 (FGF13) encodes an intracellular protein involved in microtubule stabilization and regulation of voltage-gated sodium channels (VGSCs) function. FGF13 mutation has been identified in patients with inherent seizure, suggesting a potential association between FGF13 and the etiology of TLE. Here, we set to explore the pathological role of FGF13 in the etiology of TLE.
We found that the expression of FGF13 was increased in the cortical lesions and CA1 region of sclerotic hippocampus and correlated with the seizure frequency in TLE patients. Also, Fgf13 expression was increased in the hippocampus of chronic TLE mice generated by kainic acid (KA) injection. Furthermore, Fgf13 knockdown or overexpression was respectively found to attenuate or potentiate the effects of KA on axonal length, somatic area and the VGSCs-mediated current in the hippocampal neurons.
Taken together, these findings suggest that FGF13 is involved in the pathogenesis of TLE by modulating microtubule activity and neuronal excitability.
颞叶癫痫（TLE）是成人中最常见的耐药性癫痫，其病理机制仍有待充分阐明。成纤维细胞生长因子 13（FGF13）编码一种参与微管稳定和调节电压门控钠离子通道（VGSCs）功能的细胞内蛋白。在有内在癫痫的患者中已经发现了 FGF13 突变，这表明 FGF13 与 TLE 的病因之间存在潜在关联。在这里，我们旨在探讨 FGF13 在 TLE 病因学中的病理作用。
我们发现 FGF13 的表达在硬化海马的皮质病变和 CA1 区增加，并与 TLE 患者的癫痫发作频率相关。此外，在由海人酸（KA）注射产生的慢性 TLE 小鼠的海马中，Fgf13 的表达增加。进一步的研究发现，Fgf13 的敲低或过表达分别减弱或增强了 KA 对海马神经元轴突长度、体表面积和 VGSCs 介导电流的影响。
综上所述，这些发现表明 FGF13 通过调节微管活性和神经元兴奋性参与 TLE 的发病机制。
