| Autor: |
Dan-Chao Cai, Zhiwei Wang, Tingting Bo, Shengyao Yan, Yilin Liu, Zhaowen Liu, Zeljic, Kristina, Xiaoyu Chen, Yafeng Zhan, Xiu Xu, Yasong Du, Yingwei Wang, Jing Cang, Guang-Zhong Wang, Jie Zhang, Qiang Sun, Zilong Qiu, Shengjin Ge, Zheng Ye, Zheng Wang |
| Předmět: |
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| Zdroj: |
Journal of Neuroscience; 5/6/2020, Vol. 40 Issue 19, p3799-3814, 16p |
| Abstrakt: |
MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene-circuit-behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys -Macaca fascicularis-, 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced/J-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, M£CP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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