Wang Chien-An, Lai Ming-Chi, Lui Chun-Chung, Yang San-Nan, Tiao Mao-Meng, Hsieh Chih-Sung, Lin Hung-Hong, Huang Li-Tung
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan.
Epilepsy Behav. 2007 Nov;11(3):303-9. doi: 10.1016/j.yebeh.2007.06.016. Epub 2007 Sep 7.
An enriched environment can enhance brain recovery in animals with early-life status epilepticus (SE). The purpose of this study was to determine the effects of early-life SE on spatial memory and hippocampal extracellular signal-regulated kinase (ERK) level, and the possible therapeutic effects of the enriched environment. Rats were assigned randomly to four groups: (1) control rats (nonenriched control); (2) control rats housed in an enriched environment from Postnatal Day (P) 25 to P40 (enriched control); (3) rats in which SE was induced with lithium-pilocarpine (Li-PC) at P21 (nonenriched SE); and (4) rats in which SE was induced with Li-PC at P21 and then housed in an enriched environment from P25 to P40 (enriched SE). As adults, the rats underwent spatial learning and memory tests in the Morris water maze between P50 and P55. At P55, subsets of animals were evaluated for expression of hippocampal ERK1/2 phosphorylation immediately following completion of the Morris water maze. At ~P100, another set of animals was tested for seizure threshold. When studied as adults, only the nonenriched SE group had a spatial memory deficit. The nonenriched SE group also exhibited lower levels of phosphorylated ERK2 as compared with the nonenriched control, enriched control, and enriched SE groups. Both the nonenriched SE and enriched SE groups had reduced seizure thresholds as compared with the nonenriched control and enriched control groups. Results from this study demonstrate that an enriched environment improves spatial memory in rats subjected to early-life SE, possibly through upregulation of phosphorylated ERK2 in the hippocampus. However, an enriched environment has no effect on seizure threshold.
丰富的环境可促进早年发生癫痫持续状态（SE）的动物的脑恢复。本研究的目的是确定早年SE对空间记忆和海马细胞外信号调节激酶（ERK）水平的影响，以及丰富环境可能的治疗作用。将大鼠随机分为四组：（1）对照大鼠（非丰富环境对照）；（2）从出生后第（P）25天至P40天饲养在丰富环境中的对照大鼠（丰富环境对照）；（3）在P21时用锂-匹罗卡品（Li-PC）诱导SE的大鼠（非丰富环境SE）；（4）在P21时用Li-PC诱导SE，然后从P25天至P40天饲养在丰富环境中的大鼠（丰富环境SE）。成年后，大鼠在P50至P55之间于莫里斯水迷宫中进行空间学习和记忆测试。在P55时，在完成莫里斯水迷宫后立即评估部分动物海马ERK1/2磷酸化的表达。在约P100时，对另一组动物进行癫痫发作阈值测试。当作为成年动物研究时，只有非丰富环境SE组存在空间记忆缺陷。与非丰富环境对照、丰富环境对照和丰富环境SE组相比，非丰富环境SE组的磷酸化ERK2水平也较低。与非丰富环境对照和丰富环境对照相比，非丰富环境SE组和丰富环境SE组的癫痫发作阈值均降低。本研究结果表明，丰富的环境可改善早年经历SE的大鼠的空间记忆，可能是通过上调海马中磷酸化ERK2实现的。然而，丰富的环境对癫痫发作阈值没有影响。
