Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice.
Serotonin rebalances cortical tuning and behavior linked to autism symptoms in 15q11-13 CNV mice.
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DOI：
10.1126/sciadv.1603001
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发表时间：
2017-06
期刊：
影响因子：
13.6
通讯作者：
Takumi T
中科院分区：
文献类型：
--
作者：
Nakai N;Nagano M;Saitow F;Watanabe Y;Kawamura Y;Kawamoto A;Tamada K;Mizuma H;Onoe H;Watanabe Y;Monai H;Hirase H;Nakatani J;Inagaki H;Kawada T;Miyazaki T;Watanabe M;Sato Y;Okabe S;Kitamura K;Kano M;Hashimoto K;Suzuki H;Takumi T
在人类15q11-13重复的小鼠模型中，发育阶段血清素增强可恢复自闭症症状。血清素是大脑皮层功能的重要调节剂，在自闭症谱系障碍（ASD）中其代谢存在缺陷。5 -羟色胺代谢如何调节皮质生理并促进ASD的病理和行为症状尚不清楚。我们发现正常的血清素水平对于维持新皮层的兴奋/抑制平衡、正确的感觉刺激调节和社会行为至关重要。相反，15q dup小鼠（具有人类15q11-13重复的ASD模型）的低血清素水平导致相同表型的损伤。在15q dup小鼠中恢复正常血清素水平揭示了成人asd相关症状子集的可逆性。这些发现表明血清素可能具有治疗离散ASD症状的潜力。
Serotonin enhancement during developmental stages restores autism symptoms in a mouse model of human 15q11-13 duplication. Serotonin is a critical modulator of cortical function, and its metabolism is defective in autism spectrum disorder (ASD) brain. How serotonin metabolism regulates cortical physiology and contributes to the pathological and behavioral symptoms of ASD remains unknown. We show that normal serotonin levels are essential for the maintenance of neocortical excitation/inhibition balance, correct sensory stimulus tuning, and social behavior. Conversely, low serotonin levels in 15q dup mice (a model for ASD with the human 15q11-13 duplication) result in impairment of the same phenotypes. Restoration of normal serotonin levels in 15q dup mice revealed the reversibility of a subset of ASD-related symptoms in the adult. These findings suggest that serotonin may have therapeutic potential for discrete ASD symptoms.