Inositol 1,4,5-trisphosphate receptor type-1 in granule cells, not in Purkinje cells, regulates the dendritic morphology of Purkinje cells through brain-derived neurotrophic factor production
Inositol 1,4,5-trisphosphate receptor type-1 in granule cells, not in Purkinje cells, regulates the dendritic morphology of Purkinje cells through brain-derived neurotrophic factor production
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DOI：
10.1523/jneurosci.3269-06.2006
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发表时间：
2006-10-18
影响因子：
5.3
通讯作者：
Mikoshiba, Katsuhiko
中科院分区：
文献类型：
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作者：
Hisatsune, Chihiro;Kuroda, Yukiko;Mikoshiba, Katsuhiko
在这里，我们显示了来自1，4，5-三磷酸肌醇受体1型基因敲除(IP(3)R1KO)小鼠的培养的浦肯野细胞表现出异常的树突形态。有趣的是，尽管IP(3)R1在浦肯野细胞中大量表达，但IP(3)R1在颗粒细胞中而不是在浦肯野细胞中负责浦肯野细胞树突的形成。我们还发现，BDNF的应用挽救了IP(3)R1KO Purkinje细胞的树突异常，而IP(3)R1KO小脑颗粒细胞因AMPA受体(AMPAR)和代谢性谷氨酸受体(MGluR)激活而增加的BDNF表达受到抑制。此外，我们还观察到IP(3)R1KO小鼠体内浦肯野细胞的树突形态和平行纤维-蒲肯野细胞(PF-PC)突触的超微结构异常。我们的结论是，AMPAR和mGluR的激活通过IP(3)R1介导的信号通路增加了小脑颗粒细胞中BDNF的表达，这可能是通过改变PF-PC的突触效应，在细胞间促进浦肯野细胞的树突状突起生长。
Here, we show that cultured Purkinje cells from inositol 1,4,5-trisphosphate receptor type 1 knock-out (IP(3)R1KO) mice exhibited abnormal dendritic morphology. Interestingly, despite the huge amount of IP(3)R1 expression in Purkinje cells, IP(3)R1 in granule cells, not in the Purkinje cells, was responsible for the shape of Purkinje cell dendrites. We also found that BDNF application rescued the dendritic abnormality of IP(3)R1KO Purkinje cells, and that the increase in BDNF expression in response to activation of AMPA receptor (AMPAR) and metabotropic glutamate receptor (mGluR) was impaired in IP(3)R1KO cerebellar granule cells. In addition, we observed abnormalities in the dendritic morphology of Purkinje cells and in the ultrastructure of parallel fiber-Purkinje cell (PF-PC) synapses in IP(3)R1KO mice in vivo. We concluded that activation of AMPAR and mGluR increases BDNF expression through IP(3)R1-mediated signaling in cerebellar granule cells, which contributes to the dendritic outgrowth of Purkinje cells intercellularly, possibly by modifying PF-PC synaptic efficacy.