NEST, Scuola Normale Superiore, Pisa, Italy; NEST Institute Nanoscience CNR, Pisa, Italy.
Sci Rep. 2011;1:45. doi: 10.1038/srep00045. Epub 2011 Jul 25.
The maturation of excitatory transmission comes about through a developmental period in which dendritic spines are highly motile and their number, form and size are rapidly changing. Surprisingly, although these processes are crucial for the formation of cortical circuitry, little is known about possible alterations of these processes in brain disease. By means of acute in vivo 2-photon imaging we show that the dynamic properties of dendritic spines of layer V cortical neurons are deeply affected in a mouse model of Rett syndrome (RTT) at a time around P25 when the neuronal phenotype of the disease is still mild. Then, we show that 24h after a subcutaneous injection of IGF-1 spine dynamics is restored. Our study demonstrates that spine dynamics in RTT mice is severely impaired early during development and suggest that treatments for RTT should be started very early in order to reestablish a normal period of spine plasticity.
兴奋性传递的成熟是通过一个发育阶段实现的,在此期间树突棘具有高度的运动性,其数量、形态和大小迅速发生变化。令人惊讶的是,尽管这些过程对于皮质回路的形成至关重要,但对于这些过程在脑部疾病中的可能改变却知之甚少。通过急性体内双光子成像,我们发现 Rett 综合征(RTT)小鼠模型中,在疾病神经元表型仍较温和的 P25 左右时,V 层皮质神经元的树突棘的动态特性受到了深刻影响。然后,我们发现 IGF-1 皮下注射 24 小时后,棘突动力学恢复。我们的研究表明,RTT 小鼠的棘突动力学在发育早期受到严重损害,并表明 RTT 的治疗应尽早开始,以重新建立正常的棘突可塑性时期。