Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum.
Adenosine A2A receptor in the monkey basal ganglia: ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum.
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DOI：
10.1002/cne.22751
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发表时间：
2012-02-15
影响因子：
2.5
通讯作者：
Smith, Yoland
中科院分区：
文献类型：
--
作者：
Bogenpohl, James W.;Ritter, Stefanie L.;Hall, Randy A.;Smith, Yoland
腺苷 A2A 受体 (A2AR) 是治疗帕金森病和其他神经系统疾病的潜在药物靶点。在啮齿动物中，A2AR 调节的治疗效果通过同时调节代谢型谷氨酸受体 5 (mGluR5) 得到改善。为了阐明介导这些治疗效果的解剖学基质，使用预包埋电子显微镜免疫组织化学对灵长类基底神经节中的 A2AR 定位进行详细、定量的超微结构分析，并评估纹状体中 A2AR/mGluR5 共定位的程度。 A2AR 免疫反应性在纹状体和外部苍白球 (GPe) 中处于最高水平。然而，猴子而非大鼠的黑质网状部 (SNr) 也具有显着水平的神经纤维 A2AR 免疫反应性。在电子显微镜水平上，纹状体 A2AR 标记最常见于突触后元件（标记元件的 58% ± 3%），而在 GPe 和 SNr 中，标记主要位于突触前（71% ± 5%）或胶质细胞（27% ± 6%）。在纹状体和苍白球结构中，假定的抑制性和兴奋性末端均表现出 A2AR 免疫反应性。纹状体 A2AR/mGluR5 共定位很常见；猴纹状体中 60-70% 的 A2AR 免疫反应性树突或棘共同表达 mGluR5。这些发现首次详细描述了 A2AR 在灵长类基底神经节中的超微结构定位，并证明 A2AR 和 mGluR5 在纹状体神经元的树突和棘中进行功能性相互作用。总之，这些数据促进了对 A2AR 调节灵长类基底神经节功能的底物的更深入了解，并可能介导其对帕金森病的治疗作用。
The adenosine A2A receptor (A2AR) is a potential drug target for the treatment of Parkinson’s disease and other neurological disorders. In rodents, the therapeutic efficacy of A2AR modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical substrate(s) through which these therapeutic benefits could be mediated, pre-embedding electron microscopy immunohistochemistry was used to conduct a detailed, quantitative ultrastructural analysis of A2AR localization in the primate basal ganglia and to assess the degree of A2AR/mGluR5 colocalization in the striatum. A2AR immunoreactivity was found at the highest levels in the striatum and external globus pallidus (GPe). However, the monkey, but not the rat, substantia nigra pars reticulata (SNr) also harbored a significant level of neuropil A2AR immunoreactivity. At the electron microscopic level, striatal A2AR labeling was most commonly localized in postsynaptic elements (58% ± 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% ± 5%) or glial (27% ± 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A2AR immunoreactivity. Striatal A2AR/mGluR5 colocalization was commonly found; 60–70% of A2AR-immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A2AR in the primate basal ganglia and demonstrate that A2AR and mGluR5 are located to interact functionally in dendrites and spines of striatal neurons. Together, these data foster a deeper understanding of the substrates through which A2AR could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism.
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DOI：
10.1038/npp.2008.144
发表时间：
2009-03
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
Azdad K;Gall D;Woods AS;Ledent C;Ferré S;Schiffmann SN
通讯作者：
Schiffmann SN
影响因子：
7.6
作者：
Coccurello, R;Breysse, N;Amalric, M
通讯作者：
Amalric, M
影响因子：
6.2
作者：
Brambilla, R;Cottini, L;Abbracchio, MP
通讯作者：
Abbracchio, MP
影响因子：
9.9
作者：
Bara-Jimenez, W;Sherzai, A;Chase, TN
通讯作者：
Chase, TN
影响因子：
5.3
作者：
Battaglia, G;Busceti, CL;Bruno, V
通讯作者：
Bruno, V