Browsing by Subject "Tyrosine 3-Monooxygenase"

Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Ranbp2 haploinsufficiency mediates distinct cellular and biochemical phenotypes in brain and retinal dopaminergic and glia cells elicited by the Parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
    (Cell Mol Life Sci, 2012-10) Cho, Kyoung-In; Searle, Kelly; Webb, Mason; Yi, Haiqing; Ferreira, Paulo A
    Many components and pathways transducing multifaceted and deleterious effects of stress stimuli remain ill-defined. The Ran-binding protein 2 (RanBP2) interactome modulates the expression of a range of clinical and cell-context-dependent manifestations upon a variety of stressors. We examined the role of Ranbp2 haploinsufficiency on cellular and metabolic manifestations linked to tyrosine-hydroxylase (TH(+)) dopaminergic neurons and glial cells of the brain and retina upon acute challenge to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a parkinsonian neurotoxin, which models facets of Parkinson disease. MPTP led to stronger akinetic parkinsonism and slower recovery in Ranbp2 (+/-) than wild-type mice without viability changes of brain TH(+)-neurons of either genotype, with the exception of transient nuclear atypia via changes in chromatin condensation of Ranbp2 (+/-) TH(+)-neurons. Conversely, the number of wild-type retinal TH(+)-amacrine neurons compared to Ranbp2 (+/-) underwent milder declines without apoptosis followed by stronger recoveries without neurogenesis. These phenotypes were accompanied by a stronger rise of EdU(+)-proliferative cells and non-proliferative gliosis of GFAP(+)-Müller cells in wild-type than Ranbp2 (+/-) that outlasted the MPTP-insult. Finally, MPTP-treated wild-type and Ranbp2 (+/-) mice present distinct metabolic footprints in the brain or selective regions thereof, such as striatum, that are supportive of RanBP2-mediated regulation of interdependent metabolic pathways of lysine, cholesterol, free-fatty acids, or their β-oxidation. These studies demonstrate contrasting gene-environment phenodeviances and roles of Ranbp2 between dopaminergic and glial cells of the brain and retina upon oxidative stress-elicited signaling and factors triggering a continuum of metabolic and cellular manifestations and proxies linked to oxidative stress, and chorioretinal and neurological disorders such as Parkinson.
  • Thumbnail Image
    ItemOpen Access
    Role of the midbrain dopaminergic system in modulation of vocal brain activation by social context.
    (Eur J Neurosci, 2007-06) Hara, Erina; Kubikova, Lubica; Hessler, Neal A; Jarvis, Erich D
    In a well-studied model of social behaviour, male zebra finches sing directed song to court females and undirected song, used possibly for practice or advertisement. Although the two song types are similar, the level of neural activity and expression of the immediate early gene egr-1 are higher during undirected than during directed singing in the lateral part of the basal ganglia song nucleus AreaX (LAreaX) and its efferent pallial song nuclei lateral magnocellular nucleus of the anterior nidopallium (LMAN) and the robust nucleus of the arcopallium (RA). As social interactions are dependent on brain motivation systems, here we test the hypothesis that the midbrain ventral tegmental area-substantia nigra pars compacta (VTA-SNc) complex, which provides a strong dopaminergic input to LAreaX, is a source of this modulation. Using egr-1 expression, we show that GABAergic interneurons in VTA-SNc are more active during directed courtship singing than during undirected singing. We also found that unilateral removal of VTA-SNc input reduced singing-dependent gene expression in ipsilateral LAreaX during both social contexts but it did not eliminate social context differences in LAreaX. In contrast, such lesions reduced and eliminated the social context differences in efferent nuclei LMAN and RA, respectively. These results suggest that VTA-SNc is not solely responsible for the social context gene regulation in LAreaX, but that VTA-SNc input to LAreaX enhances the singing-regulated gene expression in this nucleus and, either through LAreaX or through direct projections to LMAN and RA, VTA-SNc is necessary for context-dependent gene regulation in these efferent nuclei.