对老年小鼠进行预防性溶酶治疗可降低癫痫发作的严重程度并提高癫痫状态的存活率

IF 7.8 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology
Aging Cell Pub Date : 2024-06-20 DOI:10.1111/acel.14239
Tahiyana Khan, Abbas I. Hussain, Timothy P. Casilli, Logan Frayser, Michelle Cho, Gabrielle Williams, David McFall, Patrick A. Forcelli
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引用次数: 0

摘要

无论是在临床上还是在各种老龄化癫痫模型中,都有充分的证据表明老龄化患者更容易出现癫痫发作。癫痫发作会加剧认知能力的衰退,而认知能力的衰退在衰老过程中已经非常明显。衰老细胞被认为是衰老过程中认知功能受损的原因之一,使用衰老分解药物清除衰老细胞可改善动物模型的认知功能。目前仍不清楚衰老细胞是否会使衰老的大脑易受癫痫发作的影响。在这里,我们证明了达沙替尼和槲皮素(D&Q)的预防性衰老治疗可降低老年C57BL/6J小鼠癫痫发作的严重程度和死亡率。我们让 D&Q 和 VEH 处理过的老年小鼠在急性癫痫发作(癫痫状态[SE])之前和之后进行空间记忆测试,癫痫状态会导致癫痫发展。我们发现,衰老疗法能改善损伤前的空间记忆,但在癫痫状态发作后,空间记忆并没有得到恢复。衰老相关蛋白 p16 和衰老相关 β-半乳糖苷酶在 D&Q 处理的老龄小鼠中减少。我们的研究结果表明,衰老细胞会增加衰老过程中癫痫发作的易感性。因此,预防性靶向衰老细胞可预防与年龄相关的癫痫发作。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Prophylactic senolytic treatment in aged mice reduces seizure severity and improves survival from Status Epilepticus

Prophylactic senolytic treatment in aged mice reduces seizure severity and improves survival from Status Epilepticus

Prophylactic senolytic treatment in aged mice reduces seizure severity and improves survival from Status Epilepticus

Increased vulnerability to seizures in aging has been well documented both clinically and in various models of aging in epilepsy. Seizures can exacerbate cognitive decline that is already prominent in aging. Senescent cells are thought to contribute to cognitive impairment in aging and clearing senescent cells with senolytic drugs improves cognitive function in animal models. It remains unclear whether senescent cells render the aged brain vulnerable to seizures. Here, we demonstrate that prophylactic senolytic treatment with Dasatinib and Quercetin (D&Q) reduced both seizure severity and mortality in aged C57BL/6J mice. We subjected the D&Q and VEH-treated aged mice to spatial memory testing before and after an acute seizure insult, Status Epilepticus [SE], which leads to epilepsy development. We found that senolytic therapy improved spatial memory before injury, however, spatial memory was not rescued after SE. Senescence-related proteins p16 and senescence-associated β-galactosidase were reduced in D&Q-treated aged mice. Our findings indicate that senescent cells increase seizure susceptibility in aging. Thus, prophylactically targeting senescent cells may prevent age-related seizure vulnerability.

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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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