Li Hong-Bin, Mao Rong-Rong, Zhang Ji-Chuan, Yang Ya, Cao Jun, Xu Lin
Key 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.
Biol Psychiatry. 2008 Aug 15;64(4):286-92. doi: 10.1016/j.biopsych.2008.02.020. Epub 2008 Apr 11.
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.
应激被认为会加剧神经精神和认知障碍。特别是海马体，它在某些类型的记忆（包括空间记忆）中起关键作用，对应激极其敏感。某些类型的记忆被认为依赖于活动依赖的海马体突触可塑性，如长时程增强（LTP）和长时程抑制（LTD），但应激会抑制海马体中的LTP并促进LTD，损害空间记忆。尽管瞬时受体电位香草酸受体1（TRPV1或VR1）在海马体中广泛表达，但TRPV1通道是否能拮抗应激对海马体功能的影响仍不清楚。
我们使用TRPV1激动剂辣椒素和树脂毒素以及选择性拮抗剂辣椒平（capsazepine）和SB366791，研究了TRPV1激活对幼年大鼠海马体CA1区脑片LTP和LTD的影响。此外，我们还研究了海马体内或胃内注射TRPV1激动剂是否能预防急性应激对突触可塑性和空间记忆的影响。
TRPV1激动剂辣椒素和树脂毒素促进LTP但抑制LTD。这些改变是由TRPV1介导的，因为TRPV1选择性拮抗剂辣椒平和SB366791阻断了辣椒素的作用。急性应激抑制LTP并诱导LTD，但TRPV1激动剂辣椒素有效预防了这种作用。当海马体内或胃内注射辣椒素时，急性应激对空间记忆提取的损害作用被完全预防。
TRPV1通道是促进LTP和抑制LTD的潜在靶点，进而保护海马体突触可塑性和空间记忆提取免受急性应激的影响。
