Rogers B C, Barnes M I, Mitchell C L, Tilson H A
Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514.
Brain Res. 1989 Jul 24;493(1):41-50. doi: 10.1016/0006-8993(89)90998-0.
Several reports have implicated the overactivity of hippocampal glutaminergic systems in neurodegenerative conditions including Senile dementia of the Alzheimer's type (SDAT). The neurobiological effects of hippocampal glutaminergic hyperactivity were studied by perforant pathway stimulation. Forty-five minutes of sustained perforant pathway stimulation produced a 50% or greater increase in motor activity 1, 2, and 3 weeks after stimulation. Robust retention deficits in a 48-h step-through passive avoidance task were evident 2 weeks post-stimulation. Furthermore, animals receiving stimulation were impaired in the acquisition of a spatial task in the Morris water maze. Stimulated animals exhibited little reduction in their escape latencies over the testing period. The learning and memory deficits were associated with a loss of CA1 and CA3 pyramidal cells and pretreatment with the N-methyl-D-aspartate antagonist MK-801 reduced this cell loss, particularly in the CA1 region of the hippocampus. These results suggest that sustained stimulation of the perforant pathway may be useful in studying neurological deficits associated with glutaminergic hyperfunction.
多项报告表明，海马体谷氨能系统的过度活跃与包括阿尔茨海默病型老年痴呆症（SDAT）在内的神经退行性疾病有关。通过穿通通路刺激研究了海马体谷氨能亢进的神经生物学效应。持续45分钟的穿通通路刺激在刺激后1周、2周和3周使运动活动增加了50%或更多。在刺激后2周，48小时一步通过被动回避任务中明显出现了强烈的记忆保持缺陷。此外，接受刺激的动物在莫里斯水迷宫的空间任务获取方面存在障碍。在测试期间，受刺激的动物逃避潜伏期几乎没有缩短。学习和记忆缺陷与CA1和CA3锥体细胞的丧失有关，用N-甲基-D-天冬氨酸拮抗剂MK-801预处理可减少这种细胞损失，特别是在海马体的CA1区域。这些结果表明，持续刺激穿通通路可能有助于研究与谷氨能功能亢进相关的神经功能缺陷。
