Characterization of Dopaminergic System in the Striatum of Young Adult Park2 -/- Knockout Rats
PublisherNature Publishing Group
MetadataShow full item record
AbstractMutations 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).
SponsorsThis work was supported by NIH grant DA023085.
Identifier to cite or link to this itemhttps://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
- Impaired in vivo dopamine release in parkin knockout mice.
- Authors: Oyama G, Yoshimi K, Natori S, Chikaoka Y, Ren YR, Funayama M, Shimo Y, Takahashi R, Nakazato T, Kitazawa S, Hattori N
- Issue date: 2010 Sep 17
- Phenotypic characterization of recessive gene knockout rat models of Parkinson's disease.
- Authors: Dave KD, De Silva S, Sheth NP, Ramboz S, Beck MJ, Quang C, Switzer RC 3rd, Ahmad SO, Sunkin SM, Walker D, Cui X, Fisher DA, McCoy AM, Gamber K, Ding X, Goldberg MS, Benkovic SA, Haupt M, Baptista MA, Fiske BK, Sherer TB, Frasier MA
- Issue date: 2014 Oct
- Parkin deficiency exacerbate ethanol-induced dopaminergic neurodegeneration by P38 pathway dependent inhibition of autophagy and mitochondrial function.
- Authors: Hwang CJ, Kim YE, Son DJ, Park MH, Choi DY, Park PH, Hellström M, Han SB, Oh KW, Park EK, Hong JT
- Issue date: 2017 Apr
- STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson's disease.
- Authors: Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC
- Issue date: 2015 Jan 27
- Surprising behavioral and neurochemical enhancements in mice with combined mutations linked to Parkinson's disease.
- Authors: Hennis MR, Marvin MA, Taylor CM 2nd, Goldberg MS
- Issue date: 2014 Feb