生物谷报道:用培养细胞和小鼠做的新研究显示了自然界存在的“大麻素”化合物影响发育的大脑,大麻素化合物与大麻中的精神活性化合物的关系很近。这些发现也许能为过去的研究提供一个分子基础,过去的动物研究发现在怀孕期间用大麻能给后代带来永久性的认知缺陷。内源性大麻素(endocannabinoids)抑制成熟神经元发送的信号,但是它们究竟如何在发育的大脑中操作在此之前并不清楚。通过用培养的青蛙细胞以及成年小鼠做的实验,Paul Berghuis和同事发现,内源性大麻素给年轻神经元的轴突导航,随着它们的生长,帮助建立神经元到神经元的连接。(皮层神经元在离它们最终的位置相对远的先祖区生成,然后它们在发育的大脑中迁移,沿途建立连接模式。)因为来自大麻的THC和内源性大麻素激活的受体是同样的,文章作者提出,母体的大麻消费可能会打乱内源性大麻素调节健康大脑发育的自然过程。该研究结果发表在最新一期《科学》杂志上。
Fig. 1. The temporal and spatial coincidence of CB1R localization with endocannabinoid availability during corticogenesis. (A) Schemes of the telencephalon at the embryonic days indicated. Colored symbols refer to particular structures in adjoining photomicrographs. At E14.5 to 16.5 (fig. S2B), CB1R mRNA is preferentially expressed in pyramidal cells of the hippocampus (B) and cerebral cortex (C), with CB1R immunoreactivity localized to developing long-range axons, coexpressing growth-associated protein 43 (GAP43), in the intermediate zone (9) (D and E). (F) CB1R+ processes, axons emitted by pyramidal neurons, in the fimbria. A three-dimensional reconstruction of a process is depicted in a semitransparent manner. A dotted line encircles the individual profile (1) shown to the right. (2) Adjacent CB1R+ processes (dotted line) with 3,3'-diaminobenzidine (DAB)–Ni reaction end products (black) precipitating on the inner plasmalemmal surface (arrows) after the use of an antibody recognizing the C terminus of CB1R. (G) Hippocampal interneurons (arrows) express CB1R mRNA at E18.5. (H) At birth, CB1Rs are spatially associated with GABAergic axons (arrows) navigating locally in the hippocampus. (I) Reciprocally perpendicular projections of a single CB1R+ growth cone from the hilus of newborn rat hippocampus. Numbers indicate the positions of planar images. Arrowheads indicate the truncated axon. DAB precipitation fills the cytoplasm, which also contains numerous vesicles (arrows). (J) CB1Rs concentrate in growth cone particles (GCPs) relative to total cortical lysates, as shown by Western analysis. (K) DAGL predominates in the neocortex at birth and (L) is expressed by pyramidal cells. Arrows point to gold particles indicating the precise subcellular localization of DAGL . (M) Similarly, DAGLß is expressed by pyramidal cells in the neonatal cortex. (N) A putative GABAergic presynaptic bouton on a DAGLß+ dendrite is marked by arrows. (O) A CB1R+ GABAergic axon (arrows) is targeted toward a DAGLß– interneuron (*) in the hippocampus at E18.5. (P and Q) NAPE-PLD is first expressed at E18.5 and is preferentially targeted to dendritic spines (arrows) in neocortical pyramids. (R) Some vertically migrating GABAergic interneurons possess NAPE-PLD expression. Arrows denote NAPE-PLD in the leading process. Abbreviations are defined in SOM text. Scale bars, 6 µm in (H), (K), (M) to (O), (Q), and (R); 50 µmin (E); 100 µm in (B) to (D), (G), and (P); and 500 nm in (F), (I), and (L).
原文出处:
Science 25 May 2007 Vol 316, Issue 5828,
Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity
Paul Berghuis, Ann M. Rajnicek, Yury M. Morozov, Ruth A. Ross, Jan Mulder, Gabriella M. Urbán, Krisztina Monory, Giovanni Marsicano, Michela Matteoli, Alison Canty, Andrew J. Irving, István Katona, Yuchio Yanagawa, Pasko Rakic, Beat Lutz, Ken Mackie, and Tibor Harkany
Science 25 May 2007: 1212-1216.
Endocannabinoids can inhibit the growth of axons; mice without one type of cannabinoid receptor have more inhibitory neuronal inputs to cortical areas of the brain.
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