小柯机器人

美国哥伦比亚大学Anna A. Penn、Claire-Marie Vacher等研究人员合作发现，胎盘内分泌功能塑造小脑发育和社会行为。2021年8月16日，《自然—神经科学》杂志在线发表了这项成果。

研究人员发现，胎盘别孕烷醇酮（ALLO），一种孕激素衍生的GABA-A受体（GABA_AR）调节剂，以性别连锁的方式减少对神经发育的改变。一个新的条件性小鼠模型：编码ALLO合成酶的基因（akr1c14）在滋养细胞中被特异性删除，直接证明了胎盘ALLO不足导致小脑白质异常，而这种异常只与男性后代的自闭症样行为有关。在妊娠晚期单次注射ALLO或麝香酚（一种GABA_AR激动剂）可抵消这些改变。对男性和女性人类早产婴儿小脑的比较也显示出性别相关髓鞘标记的改变，表明小鼠胎盘ALLO不足和人类早产大脑发育之间有相似之处。

这项研究揭示了一种胎盘激素在塑造大脑区域和行为方面的新作用，其方式与性别有关。胎盘激素替代可能提供新的治疗机会来防止以后的神经行为紊乱。

据了解，胎盘功能受损或过早丧失已与各种神经发育障碍有关。

附：英文原文

Title: Placental endocrine function shapes cerebellar development and social behavior

Author: Vacher, Claire-Marie, Lacaille, Helene, OReilly, Jiaqi J., Salzbank, Jacquelyn, Bakalar, Dana, Sebaoui, Sonia, Liere, Philippe, Clarkson-Paredes, Cheryl, Sasaki, Toru, Sathyanesan, Aaron, Kratimenos, Panagiotis, Ellegood, Jacob, Lerch, Jason P., Imamura, Yuka, Popratiloff, Anastas, Hashimoto-Torii, Kazue, Gallo, Vittorio, Schumacher, Michael, Penn, Anna A.

Issue&Volume: 2021-08-16

Abstract: Compromised placental function or premature loss has been linked to diverse neurodevelopmental disorders. Here we show that placenta allopregnanolone (ALLO), a progesterone-derived GABA-A receptor (GABAAR) modulator, reduction alters neurodevelopment in a sex-linked manner. A new conditional mouse model, in which the gene encoding ALLO’s synthetic enzyme (akr1c14) is specifically deleted in trophoblasts, directly demonstrated that placental ALLO insufficiency led to cerebellar white matter abnormalities that correlated with autistic-like behavior only in male offspring. A single injection of ALLO or muscimol, a GABAAR agonist, during late gestation abolished these alterations. Comparison of male and female human preterm infant cerebellum also showed sex-linked myelination marker alteration, suggesting similarities between mouse placental ALLO insufficiency and human preterm brain development. This study reveals a new role for a placental hormone in shaping brain regions and behaviors in a sex-linked manner. Placental hormone replacement might offer novel therapeutic opportunities to prevent later neurobehavioral disorders.

DOI: 10.1038/s41593-021-00896-4

Source: https://www.nature.com/articles/s41593-021-00896-4

Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex