Astrocytes in adult rat brain express type 2 inositol 1,4,5-trisphosphate receptors
Astrocytes in adult rat brain express type 2 inositol 1,4,5-trisphosphate receptors
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DOI：
10.1002/glia.10085
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发表时间：
2002-07-01
期刊：
影响因子：
6.2
通讯作者：
Russell, JT
中科院分区：
文献类型：
--
作者：
Holtzclaw, LA;Pandhit, S;Russell, JT
星形胶质细胞通过传播肌醇 1,4,5-三磷酸途径引发的 Ca2+ 波来响应神经元活动。我们之前已经表明，波传播是由专门的 Ca2+ 释放位点支持的，其中许多蛋白质，包括肌醇 1,4,5-三磷酸受体 (IP3R)，以斑块形式一起出现。大鼠脑中星形胶质细胞原位表达的特定 IP3R 异构体尚不清楚，在本报告中，我们使用异构体特异性抗体对大鼠脑切片中星形胶质细胞表达的 IP3R 亚型进行免疫组织化学定位。使用针对星形胶质细胞特异性标记物 S-100beta 或 GFAP 的抗体来鉴定星形胶质细胞。双间接免疫组化显示成年大鼠大脑所有区域的星形胶质细胞仅表达IP(3)R2。高分辨率分析表明，海马星形胶质细胞具有高度分支的突起网络，这些突起具有细毛状的延伸，其中包含与突触密切接触的点状 IP(3)R2 染色斑块。这种组织让人想起培养的神经胶质细胞中发现的信号微结构域。类似地，小脑中的伯格曼神经胶质细胞突起也含有含有 IP(3)R2 染色的细毛状突起。两个脑区中含有 IP(3)R2 的星形胶质细胞突细末分支被发现与含有突触素的突触前末梢以及含有 PSD 95 的突触后密度并列。胼胝体星形胶质细胞具有细长的形态，IP(3)R2 布满突起，沿着纤维束延伸。我们的数据表明，大鼠脑星形胶质细胞中 PLC 介导的 Ca2+ 信号传导主要通过 IP(3)R2 离子通道发生。此外，含有 IP3R2 鞘突触的末端星形胶质细胞分支的解剖学排列非常适合支持神经胶质细胞对神经元活动的监测。
Astrocytes respond to neuronal activity by propagating Ca2+ waves elicited through the inositol 1,4,5-trisphosphate pathway. We have previously shown that wave propagation is supported by specialized Ca2+ release sites, where a number of proteins, including inositol 1,4,5-trisphosphate receptors (IP3R), occur together in patches. The specific IP3R isoform expressed by astrocytes in situ in rat brain is unknown, In the present report, we use isoform-specific antibodies to localize immunohistochemically the IP3R subtype expressed in astrocytes in rat brain sections. Astrocytes were identified using antibodies against the astrocyte-specific markers, S-100beta, or GFAP. Dual indirect immunohistochemistry showed that astrocytes in all regions of adult rat brain express only IP(3)R2. High-resolution analysis showed that hippocampal astrocytes are endowed with a highly branched network of processes that bear fine hair-like extensions containing punctate patches of lP(3)R2 staining in intimate contact with synapses. Such an organization is reminiscent of signaling microdomains found in cultured glial cells. Similarly, Bergmann glial cell processes in the cerebellum also contained fine hair-like processes containing IP(3)R2 staining. The IP(3)R2-containing fine terminal branches of astrocyte processes in both brain regions were found juxtaposed to presynaptic terminals containing synaptophysin as well as PSD 95-containing postsynaptic densities. Corpus callosum astrocytes had an elongated morphology with IP(3)R2 studded processes extending along fiber tracts. Our data suggest that PLC-mediated Ca2+ signaling in astrocytes in rat brain occurs predominantly through IP(3)R2 ion channels. Furthermore, the anatomical arrangement of the terminal astrocytic branches containing IP3R2 ensheathing synapses is ideal for supporting glial monitoring of neuronal activity.