Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases
Ethanol-induced impairment of spatial memory and brain matrix metalloproteinases
复制标题
DOI：
10.1016/s0006-8993(02)04036-2
复制
发表时间：
2003-02
期刊：
影响因子：
2.9
通讯作者：
J. Wright;Alex J Masino;Jennifer R Reichert;Gary D Turner;Starla E. Meighan;P. Meighan;J. Harding
中科院分区：
文献类型：
--
作者：
J. Wright;Alex J Masino;Jennifer R Reichert;Gary D Turner;Starla E. Meighan;P. Meighan;J. Harding
空间记忆的形成似乎依赖于一个完整的海马能够与突触重塑相关的特定的生化变化。海马损伤导致突触重塑和空间记忆任务的获得中断。乙醇也会破坏正常的海马功能和空间记忆。本研究建立了乙醇处理和空间记忆障碍之间的剂量-反应关系，使用圆形水迷宫任务测量。与1 g/kg剂量和0.15 M NaCl溶剂对照处理相比，1.5和2 g/kg的腹膜内乙醇剂量显著增加了发现浸没基座的潜伏期和游泳距离。在获得的第2、4和6天，处死动物，并从海马、前额叶新皮质和小脑保留脑组织用于测量基质金属蛋白酶（MMP）。结果表明，乙醇处理干扰MMP-9，但不MMP-2，在海马的活性，并在较小程度上在前额皮质。未测量到小脑的变化。MMP活性的升高似乎是细胞外基质细胞粘附分子重构的先决条件，细胞外基质细胞粘附分子被认为在突触可塑性的过程中是重要的，这反过来似乎是必要的记忆巩固。因此，乙醇诱导的空间记忆任务的收购损害，部分可能是由于大脑MMP活性的中断。
The formation of spatial memory appears to be dependent upon an intact hippocampus capable of the specific biochemical changes associated with synaptic remodeling. Hippocampal damage results in the disruption of synaptic remodeling and the acquisition of spatial memory tasks. Ethanol also disrupts normal hippocampal functioning and spatial memory. The present investigation established a dose–response relationship between ethanol treatment and impairment of spatial memory as measured using the circular water maze task. Intraperitoneal ethanol doses of 1.5 and 2 g/kg significantly increased the latency and distance swam to find the submerged pedestal as compared with a 1 g/kg dose, and 0.15 M NaCl vehicle control treatments. On days 2, 4, and 6 of acquisition animals were sacrificed and brain tissues were retained from the hippocampus, prefrontal neocortex, and cerebellum for measurement of matrix metalloproteinases (MMPs). The results indicated that ethanol treatment interfered with MMP-9, but not MMP-2, activity in the hippocampus, and to a lesser degree in the prefrontal cortex. No changes in the cerebellum were measured. Elevations in MMP activity appear to be a prerequisite to reconfiguration of extracellular matrix cell adhesion molecules thought to be important in the process of synaptic plasticity, which in turn appears to be necessary for memory consolidation. Thus, ethanol-induced impairment in the acquisition of spatial memory tasks may, in part, be due to disruption of brain MMP activity.