Yu Xiu, Yang Han, Lv HongJie, Lu Haimei, Zhao Huawei, Xu Zhenghao
Laboratory of Rheumatology & Institute of TCM Clinical Basic Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, No.548 Binwen Road, Hangzhou, Zhejiang, 310053, China.
Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Mol Neurobiol. 2024 Aug;61(8):5601-5613. doi: 10.1007/s12035-024-03934-x. Epub 2024 Jan 12.
Although numerous studies have acknowledged disparities in epilepsy-related disease processes between young and aged animals, little is known about how epilepsy changes from young adulthood to middle age. This study investigates the impact of aging on 6-Hz corneal kindling in young-adult mice and middle-aged mice. We found that the kindling acquisition of the 6-Hz corneal kindling model was delayed in middle-aged mice when compared to young-adult mice. While the seizure stage and incidence of generalized seizures (GS) were similar between the two age groups, the duration of GS in the kindled middle-aged mice was shorter than that in the kindled young-adult mice. Besides, all kindled mice, regardless of age, were resistant to phenytoin sodium (PHT), valproate sodium (VPA), and lamotrigine (LGT), whereas middle-aged mice exhibited higher levetiracetam (LEV) resistance compared to young-adult mice. Both age groups of kindled mice displayed hyperactivity and impaired memory, which are common behavioral characteristics associated with epilepsy. Furthermore, middle-aged mice displayed more pronounced astrogliosis in the hippocampus. Additionally, the expression of Brain-Derived Neurotrophic Factor (BDNF) was lower in middle-aged mice than in young-adult mice prior to kindling. These data demonstrate that both the acquisition and expression of 6-Hz corneal kindling are attenuated in middle-aged mice, while hippocampal astrogliosis and pharmacological resistance are more pronounced in this age group. These results underscore the importance of considering age-related factors when utilizing the 6-Hz corneal kindling model in mice of varying age groups.
尽管众多研究已经认识到幼年和老年动物在癫痫相关疾病过程中存在差异，但对于癫痫如何从青年期转变为中年期却知之甚少。本研究调查了衰老对青年小鼠和中年小鼠6赫兹角膜点燃的影响。我们发现，与青年小鼠相比，中年小鼠6赫兹角膜点燃模型的点燃获得延迟。虽然两个年龄组的癫痫发作阶段和全身性癫痫发作（GS）的发生率相似，但点燃的中年小鼠的GS持续时间比点燃的青年小鼠短。此外，所有点燃的小鼠，无论年龄大小，对苯妥英钠（PHT）、丙戊酸钠（VPA）和拉莫三嗪（LGT）均耐药，而中年小鼠与青年小鼠相比，对左乙拉西坦（LEV）的耐药性更高。两个年龄组的点燃小鼠均表现出多动和记忆受损，这是与癫痫相关的常见行为特征。此外，中年小鼠在海马体中表现出更明显的星形胶质细胞增生。另外，在点燃前，中年小鼠中脑源性神经营养因子（BDNF）的表达低于青年小鼠。这些数据表明，中年小鼠6赫兹角膜点燃的获得和表达均减弱，而该年龄组海马体星形胶质细胞增生和药理耐药性更为明显。这些结果强调了在不同年龄组的小鼠中使用6赫兹角膜点燃模型时考虑年龄相关因素的重要性。
