海马区在事实、事件、空间位置等记忆中发挥着关键作用，科学家们认为其细胞分子机理是依赖于海马突触可塑性(synaptic plasticity)，即神经细胞间信息传递效能的长时增强(long-term potentiation，LTP)或长时降低(long-term depression，LTD)。应激损伤这些类型记忆的机制可能是通过损伤LTP(Foy MR,Behav Neural Biol 1987)但易化海马LTD(Xu L，Nature 1997; PNAS 1998)来实现的。
中国科学院昆明动物所动物模型与人类疾病机理重点实验室徐林研究员指导的博士研究生李红斌、毛榕榕等利用辣椒素等物质激活海马神经细胞膜上的辣椒素受体（transient receptor potential vanilloid 1，TRPV1 or VR1)，能增强海马LTP，但阻断海马LTD。辣椒素的效应不仅在TRPV1基因敲除的小鼠中缺乏，而且能被TRPV1的拮抗剂阻断；应激损伤的海马LTP和易化的海马LTD能被辣椒素逆转。行为学实验表明，通过脑室注射或灌胃给予辣椒素，动物并没有任何不适反应，此时应激损伤的空间记忆提取能被辣椒素逆转。这一发现提示，摄食辣椒可能对于生活应激事件导致的脑损伤具有保护作用，而TRPV1受体可能成为一个新靶点用于研究和开发有效的新药实现预防和治疗应激导致的神经精神疾病和认知障碍。该发现已经在爱思唯尔期刊《生物精神病学》（Biological Psychiatry 64(4):286-292，2008. IF=8.45）杂志上发表。
Biological Psychiatry，Volume 64, Issue 4, 15 August 2008, Pages 286-292，Hong-Bin Li，Lin Xu
Antistress Effect of TRPV1 Channel on Synaptic Plasticity and Spatial Memory
Hong-Bin Lia, Rong-Rong Maoa, Ji-Chuan Zhanga, Ya Yanga, Jun Caoa and Lin Xua, b, ,
aKey Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Chinese Academy of Sciences, Kunming, People's Republic of China bMental Health Institute, the Second Hospital of Central South University, Changsha, People's Republic of China.
Stress is believed to exacerbate neuropsychiatric and cognitive disorders. In particular, the hippocampus, which plays critical roles in certain types of memory, including spatial memory, is exquisitely sensitive to stress. Certain types of memory are believed to depend on activity-dependent hippocampal synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD), but stress suppresses LTP and facilitates LTD in the hippocampus and impairs spatial memory. Although the transient receptor potential vanilloid 1 (TRPV1 or VR1) is widely expressed in the hippocampus, it remains unknown whether the TRPV1 channel antagonizes the stress effects on hippocampal function.
Using the TRPV1 agonists capsaicin and resiniferatoxin and selective antagonists capsazepine and SB366791, we examined the effect of TRPV1 activation on LTP and LTD in hippocampal CA1 slices of juvenile rats. Furthermore, we examined whether the effects of acute stress on synaptic plasticity and spatial memory could be prevented by intrahippocampal or intragastric infusion of a TRPV1 agonist.
The TRPV1 agonists capsaicin and resiniferatoxin facilitated LTP but suppressed LTD. Alterations were mediated by TRPV1 because the TRPV1 selective antagonists capsazepine and SB366791 blocked the actions of capsaicin. Acute stress suppressed LTP and enabled LTD, but the TRPV1 agonist capsaicin effectively prevented this effect. When capsaicin was intrahippocampally or intragastrically infused, the acute stress effect on impairing spatial memory retrieval was completely prevented.
The TRPV1 channel is a potential target to facilitate LTP and suppress LTD, in turn protecting hippocampal synaptic plasticity and spatial memory retrieval from the influence of acute stress. [标签:content1][标签:content2]
作者:admin@医学,生命科学 2011-03-11 05:14