Roles of mTOR in neuronal development, synaptic plasticity and learning and memory

在结节性硬化症和自闭症等人类神经系统疾病中发现mTOR通路的异常激活。为了确定mTOR在神经元中的功能，我们建立了具有结构性活性mTOR突变体的转基因小鼠并进行了分析。前脑特异性活性mTOR转基因小鼠表现出癫痫发作和神经变性。小脑浦肯野细胞mTOR通路的激活可导致神经元形态和突触消除的异常。这些结果将为深入了解人类疾病的致病机制提供依据。

Aberrant activation of mTOR pathway has been found in many human neurological diseases such as tuberous sclerosis and autism. To determine mTOR function in neurons, transgenic mice having constitutively active mTOR mutant were generated and analyzed. Forebrain-specific active mTOR transgenic mice displayed epileptic seizure and neurodegeneration. Abnormalities of both neuronal morphology and synapse elimination were induced by the activation of mTOR pathway in cerebellar Purkinje cells. These results will provide insights into pathogenic mechanisms of human diseases.