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    Phenotype of striatofugal medium spiny neurons in parkinsonian and dyskinetic nonhuman primates: a call for a reappraisal of the functional organization of the basal ganglia

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    Authors
    Nadjar, Agnes
    Brotchie, Jonathan M.
    Guigoni, Celine
    Li, Qin
    Zhou, Shaobo
    Wang, Guijie
    Ravenscroft, Paula
    Georges, François
    Crossman, Alan R.
    Bezard, Erwan
    Issue Date
    2006-08-23
    Subjects
    Parkinson’s disease
    
    Metadata
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    Abstract
    The classic view of anatomofunctional organization of the basal ganglia is that striatopallidal neurons of the "indirect" pathway express D2 dopamine receptors and corelease enkephalin with GABA, whereas striatopallidal neurons of the "direct" pathway bear D1 dopamine receptors and corelease dynorphin and substance P with GABA. Although many studies have investigated the pathophysiology of the basal ganglia after dopamine denervation and subsequent chronic levodopa (L-dopa) treatment, none has ever considered the possibility of plastic changes leading to profound reorganization and/or biochemical phenotype modifications of medium spiny neurons. Therefore, we studied the phenotype of striatal neurons in four groups of nonhuman primates, including the following: normal, parkinsonian, parkinsonian chronically treated with L-dopa without exhibiting dyskinesia, and parkinsonian chronically treated with L-dopa exhibiting overt dyskinesia. To identify striatal cells projecting to external (indirect) or internal (direct) segments of the globus pallidus, the retrograde tracer cholera toxin subunit B (CTb) was injected stereotaxically into the terminal areas. Using immunohistochemistry techniques, brain sections were double labeled for CTb and dopamine receptors, opioid peptides, or the substance P receptor (NK1). We also used HPLC-RIA to assess opioid levels throughout structures of the basal ganglia. Our results suggest that medium spiny neurons retain their phenotype because no variations were observed in any experimental condition. Therefore, it appears unlikely that dyskinesia is related to a phenotype modification of the striatal neurons. However, this study supports the concept of axonal collateralization of striatofugal cells that project to both globus pallidus pars externa and globus pallidus pars interna. Striatofugal pathways are not as segregated in the primate as previously considered.
    Citation
    Nadjar A, Brotchie JM, Guigoni C, Li Q, Zhou SB, Wang GJ, Ravenscroft P, Georges F, Crossman AR, Bezard E (2006) 'Phenotype of striatofugal medium spiny neurons in parkinsonian and dyskinetic nonhuman primates: a call for a reappraisal of the functional organization of the basal ganglia', Journal of Neuroscience, 26 (34), pp.8653-8661.
    Publisher
    Society for Neuroscience
    Journal
    Journal of Neuroscience
    URI
    http://hdl.handle.net/10547/624608
    DOI
    10.1523/jneurosci.2582-06.2006
    PubMed ID
    16928853
    PubMed Central ID
    PMC6674386
    Additional Links
    https://www.jneurosci.org/content/26/34/8653
    Type
    Article
    Language
    en
    ISSN
    1529-2401
    ae974a485f413a2113503eed53cd6c53
    10.1523/jneurosci.2582-06.2006
    Scopus Count
    Collections
    Biomedical and biological science

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