Recruitment of the Sonic hedgehog signalling cascade in electroconvulsive seizure-mediated regulation of adult rat hippocampal neurogenesis.
Recruitment of the Sonic hedgehog signalling cascade in electroconvulsive seizure-mediated regulation of adult rat hippocampal neurogenesis.
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募集在电击性癫痫发作介导的成年大鼠海马神经发生调节中的声音刺猬信号级联。
DOI：
10.1111/j.1460-9568.2005.04317.x
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发表时间：
2005-10
期刊：
影响因子：
--
通讯作者：
Vaidya VA
中科院分区：
文献类型：
--
作者：
Banerjee SB;Rajendran R;Dias BG;Ladiwala U;Tole S;Vaidya VA
电惊厥发作（ECS）诱导成年哺乳动物大脑的结构重塑，包括成年海马神经发生的增加。成人海马祖细胞增殖增加的分子机制目前尚不清楚。我们假设ECS可能会招募Sonic hedgehog （Shh）通路来介导其对成人海马神经发生的影响，因为Shh可以增强神经元祖细胞的增殖，并在成人基底前脑中表达，基底前脑是向海马发送强大投射的区域。本研究表明，经环巴胺（Shh信号的一种药理抑制剂）治疗的动物，ecs诱导的成年海马祖细胞增殖的增加被完全阻断。我们的研究结果表明，急性和慢性ECS都增强了成人海马中的Shh信号，因为我们观察到Patched (Ptc) mRNA的强烈上调，Ptc是Shh受体复合物的一个组成部分，也是Shh信号的下游转录靶点。这种增加是迅速的，并且仅限于齿状回，那里是成年海马的祖先居住。此外，急性和慢性ECS均选择性地降低齿状回内Shh受体复合物的另一组分Smoothened (Smo) mRNA。然而，ECS似乎没有影响基底前脑内Shh的表达，基底前脑是Shh被顺行转运到海马体的部位。总之，我们的研究结果表明，ECS调节Shh信号级联，并表明Shh通路可能是ECS促进成人海马神经发生的重要机制。
Electroconvulsive seizure (ECS) induces structural remodelling in the adult mammalian brain, including an increase in adult hippocampal neurogenesis. The molecular mechanisms that underlie this increase in the proliferation of adult hippocampal progenitors are at present not well understood. We hypothesized that ECS may recruit the Sonic hedgehog (Shh) pathway to mediate its effects on adult hippocampal neurogenesis, as Shh is known to enhance the proliferation of neuronal progenitors and is expressed in the adult basal forebrain, a region that sends robust projections to the hippocampus. Here we demonstrate that the ECS-induced increase in proliferation of adult hippocampal progenitors was completely blocked in animals treated with cyclopamine, a pharmacological inhibitor of Shh signalling. Our results suggest that both acute and chronic ECS enhance Shh signalling in the adult hippocampus, as we observed a robust upregulation of Patched (Ptc) mRNA, a component of the Shh receptor complex and a downstream transcriptional target of Shh signalling. This increase was rapid and restricted to the dentate gyrus, where the adult hippocampal progenitors reside. In addition, both acute and chronic ECS decreased Smoothened (Smo) mRNA, the other component of the Shh receptor complex, selectively within the dentate gyrus. However, ECS did not appear to influence Shh expression within the basal forebrain, the site from which it has been suggested to be anterogradely transported to the hippocampus. Together, our findings demonstrate that ECS regulates the Shh signalling cascade and indicate that the Shh pathway may be an important mechanism through which ECS enhances adult hippocampal neurogenesis.