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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 175 (1997), S. 137-141 
    ISSN: 1573-4919
    Keywords: Pb ; dopamine biosynthesis ; tyrosine hydroxylase ; brain ; SDS-PAGE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Our previous studies have shown that exposure to low levels of Pb results in significant reductions in dopamine (DA) and its metabolites (3,4-dihyroxyphenylacetic acid, DOPAC and homovanillic acid, HVA) in nucleus acumbens (NA). This area of brain receives dopaminergic projections from the ventral tegmentum and is considered vital in manifestation of many behavioral responses. Similarly, basal and K+-induced release of DA was found significantly reduced in the Pb-exposed rats as compared to the controls in this brain region. Additional studies indicated that acute infusion of Pb in nucleus acumbens caused significant release of DA. Based on these observations it was postulated that the reductions in DA contents and in the basal and stimulus-induced release of DA in NA were manifestations of attenuated dopaminergic activity in this brain region. However, the mechanism of this attenuation is not yet clear. Studies reported here were designed to evaluate the role of a key regulatory enzy me in biosynthesis of DA, i.e. tyrosine hydroxylase (TH) in Pb-induced reductions in dopaminergic activity. The results of these studies indicated that 50 and 500 ppm Pb produced 22.8 and 56% inhibition of TH activity in vitro respectively, and that the enzyme activity was reduced to 43% in rats exposed to 50 ppm lead for 30 days as compared to the controls. The alterations in TH activity in Pb-exposed animals were further confirmed by Western blot analysis. Collectively, these results suggest that Pb-induced inhibition of TH activity in rat brain may contribute to the reductions in dopaminergic activity observed in Pb-exposed animals. (Mol Cell Biochem 175: 137–141, 1997)
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 189 (1998), S. 19-24 
    ISSN: 1573-4919
    Keywords: brain ; pb ; tyrosine hydroxylase ; SDS-PAGE
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Previous studies from our laboratory showed that subchronic exposure to low levels of Pb resulted in significant decrease in dopamine (DA) content, attenuation of stimulus-induced release of DA in the dopaminergic projection area of nucleus accumbens (NA), and alterations in tyrosine hydroxylase (TH) activity in rat whole brain homogenates. The present study reported here was conducted to assess the functional integrity of DA synthesis in different brain regions of rats subchronically (90-days) exposed to 50 ppm Pb by measuring the activity of the rate limiting enzyme, tyrosine hydroxylase, in seven brain regions. In Pb-exposed rats, TH activity was reduced in two of the seven brain regions investigated, i.e., nucleus accumbens (42% reduction) and frontal cortex (61% reduction) when compared to controls. In contrast, Pb exposure did not affect the TH activity in cerebellum, brainstem, hippocampus, hypothalamus and striatum. The changes in TH activity in nucleus accumbens (NA) and frontal cortex (FC) in Pb-exposed rats were further confirmed by Western blot analysis using TH polyclonal antibody. Collectively, these results indicate that low level subchronic Pb exposure may affect TH protein in these brain regions.
    Type of Medium: Electronic Resource
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