Dentate filter function is altered in a proepileptic fashion during aging.

Dentate filter function is altered in a proepileptic fashion during aging.
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在衰老过程中,齿状滤过功能会以诱发癫痫的方式发生改变。

DOI:
10.1111/j.1528-1167.2007.01139.x
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发表时间:
2007
期刊:
影响因子:
5.6
通讯作者:
Williamson,Anne
Williamson,Anne
中科院分区:
医学1区
文献类型:
--
作者:
Patrylo,PeterR;Tyagi,Isha;Willingham,AmyL;Lee,Sung;Williamson,Anne

文献摘要

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目的:老年人癫痫发作的发病率和患病率增加。此外,由于高达50%的这些病例没有可识别的前因,因此假设中枢神经系统本身的老化可能是致癫痫的。与成年大鼠相比,老年大鼠对与海马激活相关的癫痫发作表现出更大的易感性和严重程度。这种与年龄相关的变化是否反映了边缘系统的促惊厥变化尚不清楚,因此是本研究的重点。方法:使用电生理技术检查成年和老年Fischer 344大鼠的海马切片。齿状回是我们的模型区域,因为它涉及湿狗抖动和边缘系统癫痫发作,并且它优先受年龄的影响。结果:低频刺激引起的场电位活动组间无差异。相比之下,5-Hz分子层刺激可以在大约40%的老年切片中引起多个群体尖峰,而在成人切片中为0%。此外,在CA 3中的记录显示,这种刺激范式可以在老年人而不是成年人中引起多个尖峰,这些尖峰经常演变成自发的癫痫样爆发。这种变化的能力的齿状回响应和过滤传入输入与老化相关的减少自发IPSP的频率和增加的倾向大幅度延长EPSP后disinhibitation.Conclusions:这些癫痫的齿状回功能和电路的变化可能有助于加剧的易感性海马癫痫发作在老年啮齿动物,以及与老化相关的空间学习和记忆能力下降。
Purpose:The elderly have an increased incidence and prevalence for seizure disorders. Further, since up to 50% of these cases have no identifiable antecedent, it has been hypothesized that aging of the central nervous system itself may be epileptogenic. Aged rats, compared to adults, exhibit a greater susceptibility to and severity of seizures associated with hippocampal activation. Whether this aging‐related change reflects proconvulsive changes in limbic circuitry is unknown and thus was the focus of this study.Methods:Hippocampal slices from adult and aged Fischer 344 rats were examined using electrophysiological techniques. The dentate gyrus was our model region since it is involved with both wet‐dog shakes and limbic seizures, and it is affected preferentially with age.Results:No differences were noted between groups in field potential activity elicited with low frequency stimulation. In contrast, 5‐Hz molecular layer stimulation could evoke multiple population spikes in approximately 40% of aged versus 0% of adult slices. Further, recording in CA3 revealed that this stimulation paradigm could elicit multiple spikes in aged, but not adult, slices that frequently evolved into spontaneous epileptiform bursts. This change in the capacity of the dentate to respond to and filter afferent input was associated with an aging‐related decrease in the frequency of spontaneous IPSPs and an increased propensity for large amplitude prolonged EPSPs following disinhibition.Conclusions:These epileptogenic changes in dentate function and circuitry could contribute to the exacerbated susceptibility for hippocampal seizures in aged rodents, as well as the aging‐related decline in spatial learning and memory.