Thrombin, a mediator of neurotoxicity and memory impairment
Thrombin, a mediator of neurotoxicity and memory impairment
复制标题
DOI：
10.1016/j.neurobiolaging.2003.07.007
复制
发表时间：
2004-07-01
影响因子：
4.2
通讯作者：
Grammas, P
中科院分区：
文献类型：
--
作者：
Mhatre, M;Nguyen, A;Grammas, P
凝血酶在阿尔茨海默病（AD）的神经炎性斑块中被发现。此外，创伤性脑损伤，其中神经元暴露于高凝血酶水平，与AD的发病率增加有关。我们的目的是确定体内施用凝血酶对认知功能和神经病理学的影响。使用放射状八臂迷宫训练大鼠，然后通过脑室内输注递送凝血酶（25或100 nM，0.25 mu/h，28天）或载体。接受100 nM凝血酶的动物表现出认知障碍，包括参考记忆缺陷和任务潜伏期增加。此外，在这些动物中检测到显著的神经病理学，如脑室扩大、TUNEL阳性细胞数量增加、星形胶质细胞增生以及磷酸化神经丝和载脂蛋白-E片段的免疫反应性增加。凝血酶引起的认知功能和心室扩大的变化被水蛭素抑制。这些发现表明，凝血酶是神经毒性和认知缺陷的介质，并表明抑制凝血酶可能是AD或头部创伤相关认知缺陷的治疗策略。(C)2003年爱思唯尔公司All rights reserved.
Thrombin has been found in neuritic plaques in Alzheimer's disease (AD). Also, traumatic brain injury, where neurons are exposed to high thrombin levels, is associated with an increased incidence of AD. Our objective was to determine the effects of thrombin administered in vivo on cognitive function and neuropathology. Rats were trained using a radial eight-arm maze and then thrombin (25 or 100 nM, 0.25 mu/h, 28 days) or vehicle was delivered via intracerebroventricular infusion. Animals that received 100 nM thrombin demonstrated cognitive impairments including deficits in reference memory and an increase in task latency. Also, significant neuropathology was detected in these animals such as enlargement of cerebral ventricles, an increased number of TUNEL-positive cells, astrogliosis, and an increase in the immumoreactivity for phosphorylated neurofilament, and apolipoprotein-E fragments. Thrombin-induced changes in cognitive function and ventricular enlargement were inhibited by hirudin. These findings demonstrate that thrombin is a mediator of neurotoxicity and cognitive deficits and suggest that inhibition of thrombin may be a treatment strategy for AD- or head trauma-associated cognitive deficits. (C) 2003 Elsevier Inc. All rights reserved.