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内源性大麻素信号在斑马鱼功能性视觉和运动发育中的重要作用。

Important role of endocannabinoid signaling in the development of functional vision and locomotion in zebrafish.

作者信息

Martella Andrea, Sepe Rosa M, Silvestri Cristoforo, Zang Jingjing, Fasano Giulia, Carnevali Oliana, De Girolamo Paolo, Neuhauss Stephan C F, Sordino Paolo, Di Marzo Vincenzo

机构信息

Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Italy.

Biology and Evolution of Marine Organisms, Stazione Zoologica Anton Dohrn, Naples, Italy.

出版信息

FASEB J. 2016 Dec;30(12):4275-4288. doi: 10.1096/fj.201600602R. Epub 2016 Sep 13.

Abstract

The developmental role of the endocannabinoid system still remains to be fully understood. Here, we report the presence of a complete endocannabinoid system during zebrafish development and show that the genes that code for enzymes that catalyze the anabolism and catabolism (mgll and dagla) of the endocannabinoid, 2-AG (2-arachidonoylglycerol), as well as 2-AG main receptor in the brain, cannabinoid receptor type 1, are coexpressed in defined regions of axonal growth. By using morpholino-induced transient knockdown of the zebrafish Daglα homolog and its pharmacologic rescue, we suggest that synthesis of 2-AG is implicated in the control of axon formation in the midbrain-hindbrain region and that animals that lack Daglα display abnormal physiological behaviors in tests that measure stereotyped movement and motion perception. Our results suggest that the well-established role for 2-AG in axonal outgrowth has implications for the control of vision and movement in zebrafish and, thus, is likely common to all vertebrates.-Martella, A., Sepe, R. M., Silvestri, C., Zang, J., Fasano, G., Carnevali, O., De Girolamo, P., Neuhauss, S. C. F., Sordino, P., Di Marzo, V. Important role of endocannabinoid signaling in the development of functional vision and locomotion in zebrafish.

摘要

内源性大麻素系统的发育作用仍有待充分了解。在此,我们报告斑马鱼发育过程中完整内源性大麻素系统的存在,并表明编码催化内源性大麻素2-AG(2-花生四烯酸甘油酯)合成代谢和分解代谢的酶(mgll和dagla)的基因,以及大脑中2-AG的主要受体大麻素受体1型,在轴突生长的特定区域共表达。通过使用吗啉代诱导的斑马鱼Daglα同源物的瞬时敲低及其药理学挽救,我们认为2-AG的合成与中脑-后脑区域轴突形成的控制有关,并且缺乏Daglα的动物在测量刻板运动和运动感知的测试中表现出异常的生理行为。我们的结果表明,2-AG在轴突生长中已确立的作用对斑马鱼的视觉和运动控制有影响,因此可能在所有脊椎动物中都很常见。-马尔泰拉,A.,塞佩,R.M.,西尔维斯特里,C.,臧,J.,法萨诺,G.,卡尔内瓦利,O.,德吉罗拉莫,P.,诺豪斯,S.C.F.,索尔迪诺,P.,迪·马尔佐,V.内源性大麻素信号在斑马鱼功能性视觉和运动发育中的重要作用。

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