9-四氢大麻酚的海马神经毒性
Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol.
作者信息
Chan G C, Hinds T R, Impey S, Storm D R
机构信息
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
出版信息
J Neurosci. 1998 Jul 15;18(14):5322-32. doi: 10.1523/JNEUROSCI.18-14-05322.1998.
Abstract
Marijuana consumption elicits diverse physiological and psychological effects in humans, including memory loss. Here we report that Delta9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, is toxic for hippocampal neurons. Treatment of cultured neurons or hippocampal slices with THC caused shrinkage of neuronal cell bodies and nuclei as well as genomic DNA strand breaks, hallmarks of neuronal apoptosis. Neuron death induced by THC was inhibited by nonsteroidal anti-inflammatory drugs, including indomethacin and aspirin, as well as vitamin E and other antioxidants. Furthermore, treatment of neurons with THC stimulated a significant increase in the release of arachidonic acid. We hypothesize that THC neurotoxicity is attributable to activation of the prostanoid synthesis pathway and generation of free radicals by cyclooxygenase. These data suggest that some of the memory deficits caused by cannabinoids may be caused by THC neurotoxicity.
摘要
吸食大麻会在人体中引发多种生理和心理效应，包括记忆丧失。在此我们报告，大麻的主要精神活性成分Δ9-四氢大麻酚（THC）对海马神经元有毒性。用THC处理培养的神经元或海马切片会导致神经元细胞体和细胞核萎缩以及基因组DNA链断裂，这些都是神经元凋亡的标志。THC诱导的神经元死亡受到非甾体抗炎药（包括吲哚美辛和阿司匹林）以及维生素E和其他抗氧化剂的抑制。此外，用THC处理神经元会刺激花生四烯酸的释放显著增加。我们推测，THC的神经毒性归因于前列腺素合成途径的激活和环氧化酶产生的自由基。这些数据表明，大麻素引起的一些记忆缺陷可能是由THC的神经毒性所致。
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