Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.
Δ9-THC-caused synaptic and memory impairments are mediated through COX-2 signaling.
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DOI：
10.1016/j.cell.2013.10.042
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发表时间：
2013-11-21
期刊：
影响因子：
64.5
通讯作者：
Chen C
中科院分区：
文献类型：
--
作者：
Chen R;Zhang J;Fan N;Teng ZQ;Wu Y;Yang H;Tang YP;Sun H;Song Y;Chen C
几千年来，大麻一直被用来治疗疾病。然而，其不良的副作用限制了其医学价值。在这里，我们表明，反复暴露于Δ9-tetrahydrocannabinol （Δ9-THC）后的突触和认知障碍与环氧化酶-2 （COX-2）的诱导有关，环氧化酶-2是一种将花生四烯酸转化为前列腺素的诱导酶。Δ9-THC通过CB1受体偶联g蛋白βγ亚基介导COX-2诱导。COX-2的药理学或遗传抑制可阻断反复Δ9-THC暴露诱导的谷氨酸受体亚基的下调和内化以及海马神经元树突棘密度的改变。COX-2的消融也消除了Δ9-THC-impaired海马长期突触可塑性、空间和恐惧记忆。重要的是，在抑制COX-2的情况下，通过Δ9-THC减少阿尔茨海默病动物的β-淀粉样蛋白斑块和神经变性的有益作用仍然存在。这些结果表明，同时抑制COX-2将扩大医用大麻的适用性。
Marijuana has been used for thousands of years as a treatment for medical conditions. However, untoward side effects limit its medical value. Here we show that synaptic and cognitive impairments following repeated exposure to Δ9-tetrahydrocannabinol (Δ9-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids, in the brain. COX-2 induction by Δ9-THC is mediated via CB1 receptor-coupled G-protein βγ subunits. Pharmacological or genetic inhibition of COX-2 blocks down-regulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ9-THC exposures. Ablation of COX-2 also eliminates Δ9-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories. Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ9-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition. These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.
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DOI：
10.1007/978-3-540-88955-7_6
发表时间：
2009-01-01
期刊：
BEHAVIORAL NEUROBIOLOGY OF THE ENDOCANNABINOID SYSTEM
影响因子：
--
作者：
Alger, Bradley E.
通讯作者：
Alger, Bradley E.
影响因子：
16.2
作者：
Delaney, Andrew J.;Crane, James W.;Sah, Pankaj
通讯作者：
Sah, Pankaj
影响因子：
--
作者：
Dave, Kathleen A.;Platel, Jean-Claude;Bordey, Angelique
通讯作者：
Bordey, Angelique
影响因子：
2
作者：
Hoffman, Alexander F.;Oz, Murat;Lupica, Carl R.
通讯作者：
Lupica, Carl R.
影响因子：
4.8
作者：
Brock, TG;McNish, RW;Peters-Golden, M
通讯作者：
Peters-Golden, M