Department of Psychology and Neuroscience, Duke University, Durham, North Carolina, USA.
Hippocampus. 2011 Jun;21(6):584-608. doi: 10.1002/hipo.20783. Epub 2010 Mar 15.
Status epilepticus (SE) in adulthood dramatically alters the hippocampus and produces spatial learning and memory deficits. Some factors, like environmental enrichment and exercise, may promote functional recovery from SE. Prenatal choline supplementation (SUP) also protects against spatial memory deficits observed shortly after SE in adulthood, and we have previously reported that SUP attenuates the neuropathological response to SE in the adult hippocampus just 16 days after SE. It is unknown whether SUP can ameliorate longer-term cognitive and neuropathological consequences of SE, whether repeatedly engaging the injured hippocampus in a cognitive task might facilitate recovery from SE, and whether our prophylactic prenatal dietary treatment would enable the injured hippocampus to more effectively benefit from cognitive rehabilitation. To address these issues, adult offspring from rat dams that received either a control (CON) or SUP diet on embryonic days 12-17 first received training on a place learning water maze task (WM) and were then administered saline or kainic acid (KA) to induce SE. Rats then either remained in their home cage, or received three additional WM sessions at 3, 6.5, and 10 weeks after SE to test spatial learning and memory retention. Eleven weeks after SE, the brains were analyzed for several hippocampal markers known to be altered by SE. SUP attenuated SE-induced spatial learning deficits and completely rescued spatial memory retention by 10 weeks post-SE. Repeated WM experience prevented SE-induced declines in glutamic acid decarboxylase (GAD) and dentate gyrus neurogenesis, and attenuated increased glial fibrilary acidic protein (GFAP) levels. Remarkably, SUP alone was similarly protective to an even greater extent, and SUP rats that were water maze trained after SE showed reduced hilar migration of newborn neurons. These findings suggest that prophylactic SUP is protective against the long-term cognitive and neuropathological effects of KA-induced SE, and that rehabilitative cognitive enrichment may be partially beneficial.
成人癫痫持续状态（SE）会显著改变海马体，并导致空间学习和记忆缺陷。一些因素，如环境丰富和运动，可能促进 SE 后的功能恢复。产前胆碱补充（SUP）也可以预防成年后 SE 后短期观察到的空间记忆缺陷，我们之前的研究报告表明，SUP 可以减轻 SE 后 16 天成年海马体的神经病理学反应。目前尚不清楚 SUP 是否可以改善 SE 的长期认知和神经病理学后果，是否反复让受伤的海马体参与认知任务可以促进 SE 的恢复，以及我们的预防性产前饮食治疗是否可以使受伤的海马体更有效地受益于认知康复。为了解决这些问题，来自母鼠在胚胎第 12-17 天接受对照（CON）或 SUP 饮食的大鼠后代首先接受空间学习水迷宫任务（WM）的训练，然后给予生理盐水或海人酸（KA）诱导 SE。然后，大鼠要么留在自己的笼子里，要么在 SE 后 3、6.5 和 10 周接受三次额外的 WM 训练，以测试空间学习和记忆保留。SE 后 11 周，分析了几个已知被 SE 改变的海马体标志物。SUP 减轻了 SE 引起的空间学习缺陷，并完全挽救了 SE 后 10 周的空间记忆保留。重复 WM 经验防止了 SE 引起的谷氨酸脱羧酶（GAD）和齿状回神经发生减少，并减轻了星形胶质细胞纤维酸性蛋白（GFAP）水平的升高。值得注意的是，SUP 单独使用具有更大的保护作用，并且 SE 后接受 WM 训练的 SUP 大鼠显示新生神经元的 hilar 迁移减少。这些发现表明预防性 SUP 对 KA 诱导的 SE 的长期认知和神经病理学影响具有保护作用，而康复认知丰富可能具有部分益处。
Epilepsia. 2009-8-8
Epilepsy Res. 2007-1
Front Cell Neurosci. 2021-12-14
Nutrients. 2017-7-28
Nan Fang Yi Ke Da Xue Xue Bao. 2017-5-20
Proc Natl Acad Sci U S A. 2009-4-28
Neurotherapeutics. 2009-4
Zotero 插件