Salzberg Michael, Kumar Gaurav, Supit Laureen, Jones Nigel C, Morris Margaret J, Rees Sandra, O'Brien Terence J
Department of Psychiatry, University of Melbourne, and St. Vincent's Mental Health Service, St. Vincent's Hospital, Melbourne, Fitzroy, Victoria 3065, Australia.
Epilepsia. 2007 Nov;48(11):2079-85. doi: 10.1111/j.1528-1167.2007.01246.x.
Early life stress has enduring behavioral and neuroendocrine effects, particularly in hippocampus and amygdala. This may be relevant to mesial temporal lobe epilepsy (MTLE) that arises from these structures. In rats, we tested the hypothesis that early postnatal stress, in the form of maternal separation (MS), creates vulnerability to limbic epileptogenesis in adult life.
On postnatal days 2-14, we exposed male and female nonepileptic rats to either MS for 180 min/day, or early handling (EH) and brief separation (15 min/day). At 7 weeks of age, rats of both genders exposed to MS displayed significantly increased anxiety, as evidenced by reduced time spent in the open arms of the elevated plus maze compared with EH rats. For epileptogenesis experiments, separate cohorts of rats, similarly exposed to either early life MS or EH, were implanted with bipolar electrodes into the left amygdala and one week later rapid electrical kindling performed until fully kindled (five Class V seizures, Racine scale).
In females, fewer stimulations were required following MS than EH to reach the fully kindled state (39.6 +/- 6.4 vs. 67.1 +/- 9.4; p < 0.0001); no differences were observed in males (MS: 49.1 +/- 5.1; EH: 53.7 +/- 6.6 stimulations).
We conclude that, while postnatal MS stress increases anxiety in both genders, this early life stressor results in persisting vulnerability to limbic epileptogenesis only in females. This has implications for human MTLE and its psychiatric comorbidities, suggesting a common causation model and the involvement of gender-specific factors such as sex hormones.
早年应激具有持久的行为和神经内分泌影响，尤其是在海马体和杏仁核中。这可能与源自这些结构的内侧颞叶癫痫（MTLE）相关。在大鼠中，我们测试了这样一个假设，即产后早期应激以母婴分离（MS）的形式会使成年后易患边缘性癫痫发作。
在出生后第2 - 14天，我们将雄性和雌性非癫痫大鼠暴露于每天180分钟的母婴分离（MS），或早期抚摸（EH）及短暂分离（每天15分钟）。在7周龄时，暴露于母婴分离的两性大鼠均表现出焦虑显著增加，与早期抚摸组大鼠相比，高架十字迷宫开放臂停留时间减少证明了这一点。对于癫痫发作实验，将另一组同样暴露于早年母婴分离或早期抚摸的大鼠植入双极电极至左侧杏仁核，一周后进行快速电点燃直至完全点燃（拉辛量表五级发作5次）。
在雌性大鼠中，母婴分离组比早期抚摸组达到完全点燃状态所需的刺激次数更少（39.6±6.4 次 vs. 67.1±9.4 次；p < 0.0001）；雄性大鼠中未观察到差异（母婴分离组：49.1±5.1次；早期抚摸组：53.7±6.6次刺激）。
我们得出结论，虽然产后母婴分离应激会增加两性的焦虑，但这种早年应激源仅使雌性大鼠持续易患边缘性癫痫发作。这对人类内侧颞叶癫痫及其精神共病具有启示意义，提示存在共同的病因模型以及性别特异性因素如性激素的参与。
