Holmes Gregory L, Yang Yili, Liu Zhao, Cermak Jennifer M, Sarkisian Matthew R, Stafstrom Carl E, Neill John C, Blusztajn Jan K
Department of Neurology, Center for Research in Pediatric Epilepsy, Harvard Medical School, Children's Hospital, Hunnewell 2, 300 Longwood Avenue, Boston, MA 02115, USA.
Epilepsy Res. 2002 Jan;48(1-2):3-13. doi: 10.1016/s0920-1211(01)00321-7.
Prenatal choline supplementation can protect rats against cognitive deficits induced by status epilepticus induced by the cholinergic agent pilocarpine [J. Neurosci. 20 (2000) 1]. In the present day, we have extended this novel finding by investigating the effects of pre- and postnatal choline supplementation in memory deficits associated with status epilepticus induced with kainic acid (KA). In the first experiment pregnant rats received a normal, choline-supplemented, or choline deficient diet starting on the 11th day of gestation and continuing until postnatal (P) 7. At P42, rats were given a convulsant dosage of KA. Two weeks following the KA-induced status epilepticus rats underwent testing of visual-spatial memory using the Morris water maze test. Rats receiving supplemental choline performed better in the water maze than the deficient and control groups. Moreover, the activity of hippocampal choline acetyltransferase was 18% lower in the choline deficient animals as compared with the other two groups. In the second experiment we administered KA to P35 rats that had been given a normal diet. Following the status epilepticus the rats were given a choline-supplemented or control diet for 4 weeks and then tested in the water maze. Rats receiving choline supplementation performed far better than rats receiving a regular diet. This study demonstrates that choline supplementation prior to or following KA-induced status epilepticus can protect rats from memory deficits induced by status epilepticus.
产前补充胆碱可保护大鼠免受由胆碱能药物毛果芸香碱诱发的癫痫持续状态所导致的认知缺陷[《神经科学杂志》20 (2000) 1]。如今,我们通过研究产前和产后补充胆碱对与 kainic 酸(KA)诱发的癫痫持续状态相关的记忆缺陷的影响,扩展了这一新颖的发现。在第一个实验中,怀孕大鼠从妊娠第11天开始接受正常、补充胆碱或缺乏胆碱的饮食,并持续至出生后(P)7天。在P42时,给大鼠注射惊厥剂量的KA。KA诱发癫痫持续状态两周后,使用莫里斯水迷宫试验对大鼠的视觉空间记忆进行测试。接受补充胆碱的大鼠在水迷宫中的表现优于缺乏胆碱组和对照组。此外,与其他两组相比,胆碱缺乏动物海马胆碱乙酰转移酶的活性低18%。在第二个实验中,我们给食用正常饮食的P35大鼠注射KA。癫痫持续状态后,给大鼠补充胆碱或对照饮食4周,然后在水迷宫中进行测试。接受胆碱补充的大鼠表现远优于接受常规饮食的大鼠。这项研究表明,在KA诱发癫痫持续状态之前或之后补充胆碱可以保护大鼠免受癫痫持续状态所导致的记忆缺陷。