生物谷报道：科学家用小鼠进行的一项最新研究表明，大脑自然形成的大麻素（cannabinoid）能够促进和引导胎儿与注意力和决策相关的重要脑细胞的发育。这一成果发表于5月25日的《科学》杂志。
长期以来，科学家知道，如果成人吸食了大麻，大脑特定受体蛋白会对四氢大麻酚（THC）或其他大麻素产生响应，干扰神经元之间较强联结的形成，从而影响人类大脑对信息的处理。但是，胎儿发育时大脑自然形成的内源性大麻素（endocannabinoid）的作用一直是个谜团。
来自瑞典斯德哥尔摩Karolinska研究所的神经生物学家Tibor Harkany和同事通过对小鼠胚胎脑细胞的研究发现，当大麻素浓度较高时，神经元之间用于联系和沟通的根状轴突会发生收缩和转向。Harkany表示，一旦内源性大麻素系统被激活，它就会对细胞发出引导信号，使神经元收缩并且与新的细胞发生联结。
此项研究的另一位领导者——美国印第安那大学的Ken Mackie表示，尽管胎儿大脑中分泌的内源性大麻素可以达到很高的浓度，但是它的定位和调控十分精确。与此相比，吸食大麻后THC所产生的影响是不加选择的，二者具有显著的不同。
原始出处:
Science 25 May 2007:
Vol. 316. no. 5828, pp. 1212 - 1216
DOI: 10.1126/science.1137406
Reports
Hardwiring the Brain: Endocannabinoids Shape Neuronal Connectivity
Paul Berghuis,1* Ann M. Rajnicek,2* Yury M. Morozov,3* Ruth A. Ross,2 Jan Mulder,4 Gabriella M. Urbán,5 Krisztina Monory,6 Giovanni Marsicano,6 Michela Matteoli,7 Alison Canty,4 Andrew J. Irving,8 István Katona,5 Yuchio Yanagawa,9 Pasko Rakic,3 Beat Lutz,6 Ken Mackie,10 Tibor Harkany1
The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB1 cannabinoid receptors (CB1Rs) are enriched in the axonal growth cones of -aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB1R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB1Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.
1 Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.
2 School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen Scotland AB25 2ZD, UK.
3 Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.
4 Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.
5 Laboratory of Cerebral Cortex Research, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary.
6 Department of Physiological Chemistry, Johannes Gutenberg University Mainz, D-55099 Mainz, Germany.
7 Department of Medical Pharmacology and Consiglio Nazionale della Richerche Institute of Neuroscience, University of Milan, I-20129 Milan, Italy.
8 Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland DD1 9SY, UK.
9 Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine and Solution Oriented Research for Science and Technology, Japan Science and Technology Corporation, Maebashi 371-8511, Japan.
10 Departments of Anesthesiology Physiology, and Biophysics, University of Washington, Seattle, WA 98195-6540, USA.
* These authors contributed equally to this work.
Present address: U 862 Centre de Recherche François Magendie, INSERM, Equipe AVENIR 8 Université Bordeaux 2, 146 rue Léo Saignat, F-33077 Bordeaux, France.
Present address: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
To whom correspondence should be addressed. E-mail: Tibor.Harkany@ki.se
