Bioon.com：應(yīng)激(stress)是指環(huán)境因素嚴(yán)重?cái)_亂了生物體的生理和心理穩(wěn)態(tài)。日常生活中應(yīng)激是不可避免的,，諸如體育鍛煉,、升學(xué)競(jìng)爭(zhēng)、工作壓力,、災(zāi)難事故,、病痛衰老等等。隨著科學(xué)進(jìn)步,、經(jīng)濟(jì)發(fā)展,、自然環(huán)境變遷等，應(yīng)激與腦健康和疾病的問(wèn)題必然更加突出,。美國(guó)應(yīng)激研究所幾十年的調(diào)查表明,，應(yīng)激惡化或?qū)е?0 %以上的所有疾病，包括記憶損傷和精神疾病,。
海馬區(qū)在事實(shí),、事件,、空間位置等記憶中發(fā)揮著關(guān)鍵作用，科學(xué)家們認(rèn)為其細(xì)胞分子機(jī)理是依賴(lài)于海馬突觸可塑性(synaptic plasticity),，即神經(jīng)細(xì)胞間信息傳遞效能的長(zhǎng)時(shí)增強(qiáng)(long-term potentiation,，LTP)或長(zhǎng)時(shí)降低(long-term depression，LTD),。應(yīng)激損傷這些類(lèi)型記憶的機(jī)制可能是通過(guò)損傷LTP(Foy MR,Behav Neural Biol 1987)但易化海馬LTD(Xu L,，Nature 1997; PNAS 1998)來(lái)實(shí)現(xiàn)的。
中國(guó)科學(xué)院昆明動(dòng)物所動(dòng)物模型與人類(lèi)疾病機(jī)理重點(diǎn)實(shí)驗(yàn)室徐林研究員指導(dǎo)的博士研究生李紅斌,、毛榕榕等利用辣椒素等物質(zhì)激活海馬神經(jīng)細(xì)胞膜上的辣椒素受體（transient receptor potential vanilloid 1,，TRPV1 or VR1)，能增強(qiáng)海馬LTP,，但阻斷海馬LTD。辣椒素的效應(yīng)不僅在TRPV1基因敲除的小鼠中缺乏,，而且能被TRPV1的拮抗劑阻斷,；應(yīng)激損傷的海馬LTP和易化的海馬LTD能被辣椒素逆轉(zhuǎn)。行為學(xué)實(shí)驗(yàn)表明,，通過(guò)腦室注射或灌胃給予辣椒素,，動(dòng)物并沒(méi)有任何不適反應(yīng)，此時(shí)應(yīng)激損傷的空間記憶提取能被辣椒素逆轉(zhuǎn),。這一發(fā)現(xiàn)提示,，攝食辣椒可能對(duì)于生活應(yīng)激事件導(dǎo)致的腦損傷具有保護(hù)作用，而TRPV1受體可能成為一個(gè)新靶點(diǎn)用于研究和開(kāi)發(fā)有效的新藥實(shí)現(xiàn)預(yù)防和治療應(yīng)激導(dǎo)致的神經(jīng)精神疾病和認(rèn)知障礙,。該發(fā)現(xiàn)已經(jīng)在愛(ài)思唯爾期刊《生物精神病學(xué)》（Biological Psychiatry 64(4):286-292,，2008. IF=8.45）雜志上發(fā)表。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
