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内源性大麻素或损胎儿大脑发育

摘要 : 人体自身会产生一种类似大麻的化学物质,称为内源性大麻素。奥地利研究人员发现,如果孕妇体内的内源性大麻素含量增高,胎儿的大脑发育可能会受到损害。

 人体自身会产生一种类似大麻的化学物质,称为内源性大麻素。奥地利研究人员发现,如果孕妇体内的内源性大麻素含量增高,胎儿的大脑发育可能会受到损害。

内源性大麻素或损胎儿大脑发育

奥地利维也纳医科大学的研究人员在新一期《自然—通讯》上报告说,在胎儿大脑发育过程中,蛋白Slit及其受体Robo是重要的信号分子。附着在Robo受体上的Slit可以调节神经轴突的方向控制,从而引导胎儿大脑回路的形成。

研究人员在实验中观察到,内源性大麻素通过大麻化学成分的受体CB1和CB2调节神经细胞及少突胶质细胞中Slit和Robo的含量。一旦人体的内源性大麻素含量激增,Slit和Robo就会随之大量增多,从而导致轴突方向控制的改变,这种情况就像是刮起了一场“刺激风暴”。

研究人员说,孕妇如果患有代谢疾病如肥胖症、胰岛素抵抗症等,或者羊水内外感染,极有可能出现内源性大麻素含量增高,由此可能损害胎儿的大脑发育。因此“为确保胎儿大脑的正常发育,使出现上述疾病的孕妇保持正常的内源性大麻素含量至关重要”。

原文摘要:

Endocannabinoids modulate cortical development by configuring ​Slit2/​Robo1 signalling

Alán Alpár, Giuseppe Tortoriello, Daniela Calvigioni, Micah J. Niphakis, Ivan Milenkovic,Joanne Bakker, Gary A. Cameron, János Hanics, Claudia V. Morris, János Fuzik, Gabor G. Kovacs, Benjamin F. Cravatt, John G. Parnavelas, William D. Andrews, Yasmin L. Hurd, Erik Keimpema & Tibor Harkany

Local environmental cues are indispensable for axonal growth and guidance during brain circuit formation. Here, we combine genetic and pharmacological tools, as well as systems neuroanatomy in human fetuses and mouse models, to study the role of endocannabinoid and Slit/Robo signalling in axonal growth. We show that excess ​2-arachidonoylglycerol, an endocannabinoid affecting directional axonal growth, triggers corpus callosum enlargement due to the errant ​CB1 cannabinoid receptor-containing corticofugal axon spreading. This phenotype mechanistically relies on the premature differentiation and end-feet proliferation of ​CB2R-expressing oligodendrocytes. We further show the dependence of both axonal ​Robo1 positioning and oligodendroglial ​Slit2production on cell-type-specific cannabinoid receptor activation. Accordingly, ​Robo1 and/or ​Slit2manipulation limits endocannabinoid modulation of axon guidance. We conclude that endocannabinoids can configure focal ​Slit2/​Robo1 signalling to modulate directional axonal growth, which may provide a basis for understanding impaired brain wiring associated with metabolic deficits and prenatal drug exposure.

来源: 科技日报 浏览次数:32

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