Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran.
Prog Neuropsychopharmacol Biol Psychiatry. 2021 Dec 20;111:110344. doi: 10.1016/j.pnpbp.2021.110344. Epub 2021 May 6.
Adult neurogenesis in the hippocampal dentate gyrus plays a critical role in learning and memory. Projections originating from entorhinal cortex, known as the perforant pathway, provide the main input to the dentate gyrus and promote neurogenesis. However, neuromodulators and molecular changes mediating neurogenic effects of this pathway are not yet fully understood. Here, by means of an optogenetic approach, we investigated neurogenesis and synaptic plasticity in the hippocampus of adult rats induced by stimulation of the perforant pathway. The lentiviruses carrying hChR2 (H134R)-mCherry gene under the control of the CaMKII promoter were injected into the medial entorhinal cortex region of adult rats. After 21 days, the entorhinal cortex region was exposed to the blue laser (473 nm) for five consecutive days (30 min/day). The expression of synaptic plasticity and neurogenesis markers in the hippocampus were evaluated using molecular and histological approaches. In parallel, the changes in the gene expression of insulin and its signaling pathway, trophic factors, and components of mitochondrial biogenesis were assessed. Our results showed that optogenetic stimulation of the entorhinal cortex promotes hippocampal neurogenesis and synaptic plasticity concomitant with the increased levels of insulin mRNA and its signaling markers, neurotrophic factors, and activation of mitochondrial biogenesis. These findings suggest that effects of perforant pathway stimulation on the hippocampus, at least in part, are mediated by insulin increase in the dentate gyrus and subsequently activation of its downstream signaling pathway.
成年海马齿状回中的神经发生在学习和记忆中起着关键作用。起源于内侧嗅皮层的投射，即穿通通路，为齿状回提供主要输入，并促进神经发生。然而，介导该通路神经发生作用的神经调质和分子变化尚不完全清楚。在这里，我们通过光遗传学方法研究了成年大鼠海马中穿通通路刺激诱导的神经发生和突触可塑性。携带 hChR2（H134R）-mCherry 基因的慢病毒在成年大鼠内侧嗅皮层区域受 CaMKII 启动子的控制下被注入。21 天后，连续 5 天（每天 30 分钟）将内侧嗅皮层区域暴露于蓝色激光（473nm）下。使用分子和组织学方法评估海马中突触可塑性和神经发生标志物的表达。同时，评估胰岛素及其信号通路、营养因子和线粒体生物发生成分的基因表达变化。我们的结果表明，光遗传学刺激内侧嗅皮层促进了海马的神经发生和突触可塑性，同时增加了胰岛素 mRNA 及其信号标志物、神经营养因子的水平，并激活了线粒体生物发生。这些发现表明，穿通通路刺激对海马的影响至少部分是通过齿状回中胰岛素的增加以及随后其下游信号通路的激活来介导的。
