Details

Autor(en) / Beteiligte

• Bogenpohl, James W
• Ritter, Stefanie L
• Hall, Randy A
• Smith, Yoland

Titel

Adenosine A sub(2A) receptor in the monkey basal ganglia: Ultrastructural localization and colocalization with the metabotropic glutamate receptor 5 in the striatum

Ist Teil von

• Journal of comparative neurology (1911), 2012-02, Vol.520 (3), p.570-589

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• The adenosine A sub(2A) receptor (A sub(2A)R) is a potential drug target for the treatment of Parkinson's disease and other neurological disorders. In rodents, the therapeutic efficacy of A sub(2A)R 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 A sub(2A)R localization in the primate basal ganglia and to assess the degree of A sub(2A)R/mGluR5 colocalization in the striatum. A sub(2A)R 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 A sub(2A)R immunoreactivity. At the electron microscopic level, striatal A sub(2A)R labeling was most commonly localized in postsynaptic elements (58% plus or minus 3% of labeled elements), whereas, in the GPe and SNr, the labeling was mainly presynaptic (71% plus or minus 5%) or glial (27% plus or minus 6%). In both striatal and pallidal structures, putative inhibitory and excitatory terminals displayed A sub(2A)R immunoreactivity. Striatal A sub(2A)R/mGluR5 colocalization was commonly found; 60-70% of A sub(2A)R-immunoreactive dendrites or spines in the monkey striatum coexpress mGluR5. These findings provide the first detailed account of the ultrastructural localization of A sub(2A)R in the primate basal ganglia and demonstrate that A sub(2A)R 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 A sub(2A)R could regulate primate basal ganglia function and potentially mediate its therapeutic effects in parkinsonism. J. Comp. Neurol., 2012; 520:570-589. copyright 2011 Wiley Periodicals, Inc.