Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, United States of America.
PLoS One. 2012;7(5):e38174. doi: 10.1371/journal.pone.0038174. Epub 2012 May 31.
An array of signals regulating the early stages of postnatal subventricular zone (SVZ) neurogenesis has been identified, but much less is known regarding the molecules controlling late stages. Here, we investigated the function of the activity-dependent and morphogenic microRNA miR-132 on the synaptic integration and survival of olfactory bulb (OB) neurons born in the neonatal SVZ. In situ hybridization revealed that miR-132 expression occurs at the onset of synaptic integration in the OB. Using in vivo electroporation we found that sequestration of miR-132 using a sponge-based strategy led to a reduced dendritic complexity and spine density while overexpression had the opposite effects. These effects were mirrored with respective changes in the frequency of GABAergic and glutamatergic synaptic inputs reflecting altered synaptic integration. In addition, timely directed overexpression of miR-132 at the onset of synaptic integration using an inducible approach led to a significant increase in the survival of newborn neurons. These data suggest that miR-132 forms the basis of a structural plasticity program seen in SVZ-OB postnatal neurogenesis. miR-132 overexpression in transplanted neurons may thus hold promise for enhancing neuronal survival and improving the outcome of transplant therapies.
一系列调节产后侧脑室下区 (SVZ) 神经发生早期阶段的信号已被确定，但对于控制晚期阶段的分子知之甚少。在这里，我们研究了活性依赖和形态发生的 microRNA miR-132 对在新生 SVZ 中产生的嗅球 (OB) 神经元的突触整合和存活的功能。原位杂交显示 miR-132 的表达发生在 OB 中突触整合的开始时。使用体内电穿孔，我们发现使用基于海绵的策略隔离 miR-132 会导致树突复杂性和棘密度降低，而过表达则产生相反的效果。这些影响与 GABA 能和谷氨酸能突触输入的频率变化相呼应，反映了突触整合的改变。此外，在突触整合开始时使用诱导方法及时定向过表达 miR-132 会导致新生神经元的存活率显著增加。这些数据表明，miR-132 构成了 SVZ-OB 产后神经发生中所见的结构可塑性程序的基础。因此，移植神经元中的 miR-132 过表达可能有希望增强神经元存活并改善移植治疗的效果。
