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    Characterization of Dopaminergic System in the Striatum of Young Adult Park2 -/- Knockout Rats

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    Author
    Gemechu, J.M.
    Sharma, A.
    Yu, D.
    Date
    2018
    Journal
    Scientific Reports
    Publisher
    Nature Publishing Group
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1038/s41598-017-18526-0
    Abstract
    Mutations in parkin gene (Park2) are linked to early-onset autosomal recessive Parkinson's disease (PD) and young-onset sporadic PD. Park2 knockout (PKO) rodents; however, do not display neurodegeneration of the nigrostriatal pathway, suggesting age-dependent compensatory changes. Our goal was to examine dopaminergic (DAergic) system in the striatum of 2 month-old PKO rats in order to characterize compensatory mechanisms that may have occurred within the system. The striata form wild type (WT) and PKO Long Evans male rats were assessed for the levels of DAergic markers, for monoamine oxidase (MAO) A and B activities and levels, and for the levels of their respective preferred substrates, serotonin (5-HT) and ß-phenylethylamine (ß-PEA). The PKO rats displayed lower activities of MAOs and higher levels of ß-PEA in the striatum than their WT counterparts. Decreased levels of ß-PEA receptor, trace amine-associated receptor 1 (TAAR-1), and postsynaptic DA D2 (D2L) receptor accompanied these alterations. Drug-naive PKO rats displayed normal locomotor activity; however, they displayed decreased locomotor response to a low dose of psychostimulant methamphetamine, suggesting altered DAergic neurotransmission in the striatum when challenged with an indirect agonist. Altogether, our findings suggest that 2 month-old PKO male rats have altered DAergic and trace aminergic signaling. Copyright 2018 The Author(s).
    Sponsors
    This work was supported by NIH grant DA023085.
    Keyword
    PARK2
    parkin gene
    Parkinson Disease
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85041095536&doi=10.1038%2fs41598-017-18526-0&partnerID=40&md5=4b831e0438304b561e62da7b620e6918; http://hdl.handle.net/10713/9127
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41598-017-18526-0
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