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  • 1
    ISSN: 1573-6903
    Keywords: Dopamine ; weaver ; mutant mice ; tyrosine hydroxylase ; nigrostriatal pathway
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous reports have shown that among the markers for the nigro-striatal dopamine (DA) system measured in the striatum, dopamine uptake seems to be more severely affected than the others in the weaver mutant mouse. In the present study we examined DA levels, tyrosine hydroxylase (TH) activity, and high-affinity DA uptake to determine if the DA uptake is most affected when all the measurements are made in the same striatal homogenate in the same laboratory. We found that the DA uptake activity was most altered (93% lower) compared to DA levels (68% lower) and TH activity (64% lower). The DA uptake was so low in the weaver that we could not obtain reliable kinetic parameters. For TH activity we found that the Vmax was 36% lower while the Km forl-tyrosine was 92% higher in the weaver striatum. This lower affinity for substrate suggests that the TH enzyme itself may be altered in the nigro-striatal system of the weaver mutant mouse.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Keywords: Dopamine uptake ; serotonin uptake ; striatum ; weaver mutant mouse ; mazindol binding ; citalopram binding ; autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the striatum of the homozygous weaver mutant mouse (wv/wv), dopamine content, uptake and tyrosine hydroxylase activity are decreased compared to wild-type (+/+) mice. In mice heterozygous for the weaver gene (wv/+), these dopaminergic parameters exhibit only minor reductions compared to +/+ mice. Thewv/wv striatum has recently been shown to have an increase in serotonin content. In the present study, the serotonin uptake system of the weaver striatum was investigated. Synaptosomal uptake of [3H] serotonin was determined in the dorsal portion ofwv/wv and +/+ striatum, and serotonin uptake sites were examined by the binding of [3H] citalopram in the striatum ofwv/wv, wv/+ and +/+ mice. The dopamine uptake system was also investigated in all three genotypes via the binding of [3H] mazindol. Synaptosomal uptake of [3H] serotonin was increased by 79% in the dorsal portion of thewv/wv striatum compared to that seen in the +/+ striatum. The binding of [3H] citalopram was increased by 62% in the dorsolateral and by 111% in the dorsomedial portions of thewv/wv striatum compared to +/+. [3H] Citalopram binding in thewv/+ striatum was also higher than +/+, but this increase did not reach statistical significance. Within thewv/wv striatum, [3H] mazindol binding was almost completely absent (88–89% reduction) in the dorsal portion and severely reduced in the other striatal areas. These data support the notion that the dorsal portion of thewv/wv striatum, which has the severest reduction in dopamine uptake, is hyperinnervated by serotonin fibers.
    Type of Medium: Electronic Resource
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