Cannabinoids and gene expression during brain development
Cannabinoids and gene expression during brain development
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DOI：
10.1007/bf03033314
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发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Ramos, JA
中科院分区：
文献类型：
--
作者：
Fernández-Ruiz, J;Gómez, M;Ramos, JA
大麻是西方社会最常用的非法药物，特别是在年轻人中间。甚至妇女在怀孕和哺乳期间也吸食大麻，这对其后代的发育造成各种干扰，因为像其他成瘾药物一样，大麻的精神活性成分大麻素可以穿过胎盘屏障，分泌到母乳中。通过这种方式，大麻素影响各种神经递质系统的个体发育，导致不同行为模式的变化。多巴胺和内源性阿片类物质是受围产期大麻素暴露影响更大的神经递质之一，当动物成熟时，会产生运动活动，药物寻求行为，伤害感受和其他过程的变化。这些干扰可能起源于大麻素影响两种神经递质的关键基因表达的能力，特别是酪氨酸羟化酶和阿片样物质前体脑啡肽原。此外，大麻素似乎也能够影响编码神经元-神经胶质细胞粘附分子的基因的表达，这支持大麻素对这些蛋白质参与的细胞增殖、神经元迁移或轴突伸长过程的潜在影响。为了支持这种可能性，代表大麻素作用的主要靶点的CB 1受体在某些脑区域中大量表达，例如脑室下区域，其在脑发育期间参与这些过程。最后，大麻素也可能参与脑发育过程中发生的凋亡性死亡，可能是通过影响Bcl-2/Bax系统的表达。同样支持这一选择，CB 1受体在脑发育期间在成人脑中不含这些受体的不同神经元组中瞬时表达。本文将回顾大麻素与神经发育关键基因表达相关的所有证据，试图建立未来的研究，以阐明大麻素在大脑发育过程中的表观遗传作用机制。
Cannabis is the most commonly used illicit drug in western societies, in particular among young people. It is consumed even by women during pregnancy and lactation, which result in a variety of disturbances in the development of their offspring, because, like other habit-forming drugs, cannabinoids, the psychoactive ingredients of marijuana, can cross the placental barrier and be secreted in the maternal milk. Through this way, cannabinoids affect the ontogeny of various neurotransmitter systems leading to changes in different behavioral patterns. Dopamine and endogenous opioids are among the neurotransmitters that result more affected by perinatal cannabinoid exposure, which, when animals mature, produce changes in motor activity, drug-seeking behavior, nociception and other processes. These disturbances are likely originated by the capability of cannabinoids to influence the expression of key genes for both neurotransmitters, in particular, the enzyme tyrosine hydroxylase and the opioid precursor proenkephalin. In addition, cannabinoids seem to be also able to influence the expression of genes encoding for neuron-glia cell adhesion molecules, which supports a potential influence of cannabinoids on the processes of cell proliferation, neuronal migration or axonal elongation in which these proteins are involved. In support of this possibility, CB, receptors, which represent the major targets for the action of cannabinoids, are abundantly expressed in certain brain regions, such as the subventricular areas, which have been involved in these processes during brain development. Finally, cannabinoids might also be involved in the apoptotic death that occurs during brain development, possibly by influencing the expression of the Bcl-2/Bax system. Also in support of this option, CB1 receptors are transiently expressed during brain development in different group of neurons which do not contain these receptors in the adult brain. This paper will review all evidence relating cannabinoids to the expression of key genes for neural development, trying to establish the future research addressed to elucidate the mechanisms involved in the epigenetic action of cannabinoids during brain development.