类有机物
兴奋性突触后电位
抑制性突触后电位
神经科学
生物
人脑
化学
作者
Iva Kelava,Ilaria Chiaradia,Laura Pellegrini,Alex T. Kalinka,Madeline A. Lancaster
出处
期刊:Nature
[Springer Nature]
日期:2022-01-19
卷期号:602 (7895): 112-116
被引量:47
标识
DOI:10.1038/s41586-021-04330-4
摘要
The biological basis of male–female brain differences has been difficult to elucidate in humans. The most notable morphological difference is size, with male individuals having on average a larger brain than female individuals1,2, but a mechanistic understanding of how this difference arises remains unknown. Here we use brain organoids3 to show that although sex chromosomal complement has no observable effect on neurogenesis, sex steroids—namely androgens—lead to increased proliferation of cortical progenitors and an increased neurogenic pool. Transcriptomic analysis and functional studies demonstrate downstream effects on histone deacetylase activity and the mTOR pathway. Finally, we show that androgens specifically increase the neurogenic output of excitatory neuronal progenitors, whereas inhibitory neuronal progenitors are not increased. These findings reveal a role for androgens in regulating the number of excitatory neurons and represent a step towards understanding the origin of sex-related brain differences in humans. Experiments in cerebral organoids show that sex hormones have a role in regulating the number of excitatory neurons in the human neocortex, providing insight into the mechanistic basis of sex-related brain differences in humans.
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