Seeger Thomas F, Bartlett Brenda, Coskran Timothy M, Culp Jeffrey S, James Larry C, Krull David L, Lanfear Jerry, Ryan Anne M, Schmidt Christopher J, Strick Christine A, Varghese Alison H, Williams Robert D, Wylie Patricia G, Menniti Frank S
CNS Discovery, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA.
Brain Res. 2003 Sep 26;985(2):113-26. doi: 10.1016/s0006-8993(03)02754-9.
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. Immunoreactivity 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.
PDE10A是一种新发现的环磷酸腺苷/环磷酸鸟苷磷酸二酯酶，其信使核糖核酸在哺乳动物纹状体中高表达。在本研究中，使用单克隆抗体（24F3.F11）进行蛋白质免疫印迹和免疫组织化学分析，并使用反义核糖探针进行原位杂交，测定了PDE10A蛋白和信使核糖核酸在大鼠全脑的表达情况。在纹状体复合体（尾状核、伏隔核和嗅结节）的大多数神经元细胞体中观察到高水平的信使核糖核酸，这表明PDE10A由纹状体中型多棘神经元表达。PDE10A样免疫反应在整个纹状体神经毡以及内囊、苍白球和黑质中都很密集。后几个区域缺乏PDE10A信使核糖核酸的显著表达。因此，PDE10A被转运到整个树突并沿着轴突向下到达中型多棘神经元的终末。这些数据表明PDE10A在调节纹状体黑质和纹状体苍白球通路的活性中发挥作用。此外，在海马锥体细胞层、齿状颗粒细胞层以及整个皮质和小脑颗粒细胞层中发现PDE10A免疫反应和信使核糖核酸水平较低。在这些后几个区域仅在细胞体中检测到免疫反应。PDE10A在纹状体之外更局限的亚细胞定位表明该酶在这些区域具有第二种不同的功能。
