Immunohistochemical localization of PDE10A in the rat brain

Immunohistochemical localization of PDE10A in the rat brain
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DOI:
10.1016/s0006-8993(03)02754-9
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发表时间:
2003-09-26
期刊:
影响因子:
2.9
通讯作者:
Menniti, FS
Menniti, FS
中科院分区:
医学3区
文献类型:
--
作者:
Seeger, TF;Bartlett, B;Menniti, FS

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PDE10A是一种新发现的cAMP/cGMP磷酸二酯酶,其mRNA在哺乳动物纹状体中高表达。在本研究中,采用单克隆抗体(24F3.F11)进行Western blot和免疫组化分析,反义核糖探针进行原位杂交,测定了PDE10A蛋白和mRNA在大鼠脑中的表达。纹状体复合体的大部分神经元细胞体(尾状核、伏隔核和嗅结节)中mRNA表达水平均较高,表明PDE10A在纹状体中棘神经元中表达。pde10a样免疫反应性在整个纹状体神经节,以及内囊、苍白球和黑质中都很密集。这些区域缺乏PDE10A mRNA的显著表达。因此,PDE10A通过树突树和轴突向下运输到中棘神经元的末端。这些数据表明PDE10A在调节纹状体神经通路和纹状体神经通路的活动中发挥作用。PDE10A在海马锥体细胞层、齿状颗粒细胞层以及整个皮层和小脑颗粒细胞层的免疫反应性和mRNA水平均较低。免疫活性仅在这些后一区域的细胞体中检测到。PDE10A在纹状体外的亚细胞定位更受限,这表明该酶在这些区域具有第二种独特的功能。(C) 2003 Elsevier B.V.版权所有
PDE10A is a newly identified cAMP/cGMP phosphodiesterase for which mRNA is highly expressed in the mammalian striatum. In the present study, PDE10A protein and mRNA expression throughout the rat brain were determined, using a monoclonal antibody (24F3.F11) for Western blot and immunohistochemical analyses and an antisense riboprobe for in situ hybridization. High levels of mRNA are observed in most of the neuronal cell bodies of striatal complex (caudate n, n. accumbens and olfactory tubercle), indicating that PDE10A is expressed by the striatal medium spiny neurons. PDE10A-like immunoreactivity is dense throughout the striatal neuropil, as well as in the internal capsule, globus pallidus, and substantia nigra. These latter regions lack significant expression of PDE10A mRNA. Thus, PDE10A is transported throughout the dendritic tree and down the axons to the terminals of the medium spiny neurons. These data suggest a role for PDE10A in regulating activity within both the striatonigral and striatopallidal pathways. In addition, PDE10A immunoreactivity and mRNA are found at lower levels in the hippocampal pyramidal cell layer, dentate granule cell layer and throughout the cortex and cerebellar granule cell layer. Inummoreactivity is detected only in cell bodies in these latter regions. This more restricted subcellular localization of PDE10A outside the striatum suggests a second, distinct function for the enzyme in these regions. (C) 2003 Elsevier B.V. All rights reserved.