Ror bars represent mean S.E. ANOVA, , p 0.05; , p 0.01; , p 0.001; n 3 embryos per group.ditions (Fig. 4, C and D). Moreover, in our study, Nur77deficient mice displayed no substantial variations in 24 h of residence cage activity (Fig. 3H). Equivalent groups of animals had been also treated and assessed for potential variations in DA cell survival following MPTP. Following MPTP administration, there was a significant reduction (36.7 ; p 0.001) in TH SNc neurons in WT mice (Fig. 3B). Interestingly, and consistent withMAY 17, 2013 VOLUME 288 NUMBERresults observed in culture, Nur77deficient mice displayed a significantly greater loss of TH cells than WT mice treated with MPTP (68.six ; p 0.001). This observation of improved dopaminergic neuron loss was corroborated morphologically utilizing cresyl violet staining, assessing neurons in the amount of the medial terminal nucleus (bregma, 3.tert-Butyl oct-7-yn-1-ylcarbamate Purity 16 mm) inside the SNc (Fig. 3C). Analysis was consistent with that of TH survival, showing no differenceJOURNAL OF BIOLOGICAL CHEMISTRYNur77 Expression in Dopaminergic Neuron SurvivalFIGURE 3. Nur77deficient mice display enhanced dopamine cell bodies and striatal terminals of MPTPinduced degeneration of SNc dopaminergic neurons. A, representative photomicrographs illustrating TH immunoreactivity in the ventral midbrain SNc following indicated treatments. B, quantification of TH neurons employing stereological analysis, as described below “Experimental Procedures.” C, quantification of cresyl violetstained (CV) cells on the SNc (medial terminal nucleus (MTN) level). D, representative photomicrographs of striatal THimmunoreactive sections from treated animal groups in a. E, quantification of striatal TH fiber optical density. F, representative photomicrographs of striatal DATimmunoreactive sections from treated animal groups within a. G, quantification of striatal DAT fiber optical density. H, analysis of 24h home cage locomotor activity for WT and Nur77deficient mice. Error bars represent mean S.E. ANOVA, , p 0.05; , p 0.01; , p 0.001; n 6 8 animals per group. CV, cresylviolet; OD, optical density.1040377-08-9 Purity among salinetreated groups, a important loss of TH neurons in WT MPTPtreated mice (28.PMID:23329650 7 ; p 0.001), and a important increased loss in DA neurons in Nur77deficient MPTPtreated animals (56.7 ; p 0.001). MPTP derives its toxic effects when it crosses the bloodbrain barrier and is converted to MPP , the active dopaminergic neural toxin, by monoamine oxidase B (45). The hypersensitivity observed in Nur77deficient animals could possibly be attributed to altered MPTP metabolism and thus considerable increased MPP . To examine this possibility, striatal tissue was evaluated from micemin right after a single injection of MPTP, and levels of MPP inside the striatum have been determined using HPLC. It was observed that MPP levels did not considerably differ between WT and Nur77deficient animals (66.0 5.four and 74.5 3.2, respectively, p 0.225), suggesting that the elevated sensitivity afforded by Nur77 deficiency was not resulting from impaired MPTP metabolism. Nur77deficient Mice Exhibit Elevated Degeneration of DA Terminals, Loss of Amines, and Markers of Deregulated Basal Ganglia Following MPTP TreatmentOur outcomes above indicate that MPTPinduced loss of dopaminergic cell bodies in theVOLUME 288 Number 20 Might 17,14366 JOURNAL OF BIOLOGICAL CHEMISTRYNur77 Expression in Dopaminergic Neuron SurvivalFIGURE 4. Nur77 KO mice treated with MPTP display enhanced striatal FosB, a marker for postsynaptic adjustments in the.
