Hyper-excitability and epilepsy generated by chronic early-life stress.
Hyper-excitability and epilepsy generated by chronic early-life stress.
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由慢性早期应激产生的超兴趣和癫痫。
DOI：
10.1016/j.ynstr.2015.03.001
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发表时间：
2015
影响因子：
5
通讯作者：
Baram, Tallie Z
中科院分区：
文献类型：
--
作者：
Dube, Celine M;Molet, Jenny;Singh-Taylor, Akanksha;Ivy, Autumn;Maras, Pamela M;Baram, Tallie Z
癫痫在高压力人群中更为普遍，但其神经生物学机制尚不清楚。压力是癫痫患者癫痫发作的常见诱因，可能通过多种机制引起癫痫发作，包括大脑内神经递质和激素水平的变化。重要的是，生命早期敏感时期的压力有助于“大脑编程”，影响神经元功能和大脑网络。然而，尚不清楚早期生活压力是否会影响边缘兴奋性并促进癫痫。本研究采用一种成熟的、自然的慢性早期生活应激（CES）模型，并结合分子和细胞技术，采用慢性皮层和边缘视频脑电图（ceeg）来探讨应激对年龄特异性癫痫和神经网络高兴奋性的影响，并确定其潜在机制。在对照雄性大鼠，整个发育过程中获得的脑电图正常，未观察到癫痫发作。在大多数经历CES的大鼠中，脑电图显示癫痫尖峰和尖峰系列，57%的CES大鼠发生癫痫发作：11/23（48%）发生与人类年龄特异性癫痫婴儿痉挛相似的行为事件，伴有脑电图尖峰和/或电衰减，另外两只大鼠（9%）发生涉及杏仁核的边缘癫痫发作。为了探测杏仁核内的应激依赖性内源性惊厥分子，我们检测了促惊厥神经肽促肾上腺皮质激素释放激素（CRH）的表达，发现青春期CES大鼠的杏仁核（而非皮质）CRH表达显著增加。总之，持续时间有限的CES对大脑兴奋性有长期影响，并可能促进年龄特异性发作和癫痫。虽然相关的机制需要进一步研究，但这些发现为环境对早期癫痫发作的影响提供了重要的见解。
Epilepsy is more prevalent in populations with high measures of stress, but the neurobiological mechanisms are unclear. Stress is a common precipitant of seizures in individuals with epilepsy, and may provoke seizures by several mechanisms including changes in neurotransmitter and hormone levels within the brain. Importantly, stress during sensitive periods early in life contributes to ‘brain programming’, influencing neuronal function and brain networks. However, it is unclear if early-life stress influences limbic excitability and promotes epilepsy. Here we used an established, naturalistic model of chronic early-life stress (CES), and employed chronic cortical and limbic video-EEGs combined with molecular and cellular techniques to probe the contributions of stress to age-specific epilepsies and network hyperexcitability and identify the underlying mechanisms. In control male rats, EEGs obtained throughout development were normal and no seizures were observed. EEGs demonstrated epileptic spikes and spike series in the majority of rats experiencing CES, and 57% of CES rats developed seizures: Behavioral events resembling the human age-specific epilepsy infantile spasms occurred in 11/23 (48%), accompanied by EEG spikes and/or electrodecrements, and two additional rats (9%) developed limbic seizures that involved the amygdala. Probing for stress-dependent, endogenous convulsant molecules within amygdala, we examined the expression of the pro-convulsant neuropeptide corticotropin-releasing hormone (CRH), and found a significant increase of amygdalar--but not cortical--CRH expression in adolescent CES rats. In conclusion, CES of limited duration has long-lasting effects on brain excitability and may promote age-specific seizures and epilepsy. Whereas the mechanisms involved require further study, these findings provide important insights into environmental contributions to early-life seizures.