Pten regulates neuronal arborization and social interaction in mice
Pten regulates neuronal arborization and social interaction in mice
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DOI：
10.1016/j.neuron.2006.03.023
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发表时间：
2006-05-04
期刊：
影响因子：
16.2
通讯作者：
Parada, Luis F.
中科院分区：
文献类型：
--
作者：
Kwon, Chang-Hyuk;Luikart, Bryan W.;Parada, Luis F.
在小鼠中Pten的CNS缺失揭示了其在控制细胞大小和数量中的作用，从而为大头畸形和Lhermitte-Duclos病提供了令人信服的病因学。在患有自闭症谱系障碍（ASD）的个体中也有PTEN突变的报道，尽管PTEN和ASD之间的因果关系尚不清楚。在本研究中，我们删除Pten在有限的分化的神经元群体在大脑皮层和海马的小鼠。由此产生的突变小鼠表现出异常的社会互动和对感官刺激的过度反应。我们观察到大头畸形和神经元肥大，包括肥大和异位树突和轴突束增加突触。这种异常形态与Akt/mTor/S6 k通路的激活和Gsk 3 β的失活有关。因此，我们的数据表明，在特定的神经元群体中PI 3 K/AKT通路的异常激活可以作为大头畸形和行为异常的基础，这让人联想到人类ASD的某些特征。
CNS deletion of Pten in the mouse has revealed its roles in controlling cell size and number, thus providing compelling etiology for macrocephaly and Lhermitte-Duclos disease. PTEN mutations in individuals with autism spectrum disorders (ASD) have also been reported, although a causal link between PTEN and ASD remains unclear. In the present study, we deleted Pten in limited differentiated neuronal populations in the cerebral cortex and hippocampus of mice. Resulting mutant mice showed abnormal social interaction and exaggerated responses to sensory stimuli. We observed macrocephaly and neuronal hypertrophy, including hypertrophic and ectopic dendrites and axonal tracts with increased synapses. This abnormal morphology was associated with activation of the Akt/mTor/S6k pathway and inactivation of Gsk3 beta. Thus, our data suggest that abnormal activation of the PI3K/AKT pathway in specific neuronal populations can underlie macrocephaly and behavioral abnormalities reminiscent of certain features of human ASD.