生物谷報道：科學(xué)家用小鼠進行的一項最新研究表明,，大腦自然形成的大麻素（cannabinoid）能夠促進和引導(dǎo)胎兒與注意力和決策相關(guān)的重要腦細(xì)胞的發(fā)育。這一成果發(fā)表于5月25日的《科學(xué)》雜志,。
長期以來,，科學(xué)家知道，如果成人吸食了大麻,，大腦特定受體蛋白會對四氫大麻酚（THC）或其他大麻素產(chǎn)生響應(yīng),，干擾神經(jīng)元之間較強聯(lián)結(jié)的形成，從而影響人類大腦對信息的處理,。但是,，胎兒發(fā)育時大腦自然形成的內(nèi)源性大麻素（endocannabinoid）的作用一直是個謎團。
來自瑞典斯德哥爾摩Karolinska研究所的神經(jīng)生物學(xué)家Tibor Harkany和同事通過對小鼠胚胎腦細(xì)胞的研究發(fā)現(xiàn),，當(dāng)大麻素濃度較高時,，神經(jīng)元之間用于聯(lián)系和溝通的根狀軸突會發(fā)生收縮和轉(zhuǎn)向。Harkany表示,，一旦內(nèi)源性大麻素系統(tǒng)被激活,，它就會對細(xì)胞發(fā)出引導(dǎo)信號，使神經(jīng)元收縮并且與新的細(xì)胞發(fā)生聯(lián)結(jié),。
此項研究的另一位領(lǐng)導(dǎo)者——美國印第安那大學(xué)的Ken Mackie表示,，盡管胎兒大腦中分泌的內(nèi)源性大麻素可以達到很高的濃度，但是它的定位和調(diào)控十分精確,。與此相比,，吸食大麻后THC所產(chǎn)生的影響是不加選擇的，二者具有顯著的不同,。
原始出處:
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: [email protected]
