Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for neuron aging

G. M. Pasinetti, H. H. Osterburg, A. B. Kelly, S. Kohama, D. G. Morgan, J. F. Reinhard, R. H. Stellwagen, C. E. Finch

    Research output: Contribution to journalArticle

    58 Scopus citations

    Abstract

    Slow neuron regression develops during the adult phase of life in select brain systems of mammals. We describe a model in adult rats that resolves several phases in a slow atrophic process that differentially influences levels of mRNA and protein for tyrosine hydroxylase (TH). Responses of striatal dopaminergic markers to 6-hydroxydopamine (6-OHDA) lesions in rats indicated that the striatal terminals maintained TH protein, despite >3-fold loss of TH mRNA in the substantia nigra pars compacta (SNC) cell bodies whose axons project to the striatum. The loss of TH mRNA/cell was progressive up to 9 months, whereas SNC cell body shrinkage stabilized by 3 months post-lesioning. Consideration of possible mechanisms in protein turnover motivated a search for PEST motifs in the TH of rats and other vertebrates that could be a point of regulation by altering the rate of TH protein turnover.

    Original languageEnglish (US)
    Pages (from-to)63-73
    Number of pages11
    JournalMolecular Brain Research
    Volume13
    Issue number1-2
    DOIs
    StatePublished - Mar 1992

    Keywords

    • 6-Hydroxydopamine
    • Aging
    • Basal ganglia
    • Dopamine
    • PEST sequence
    • Tyrosine hydroxylase
    • mRNA regulation

    ASJC Scopus subject areas

    • Molecular Biology
    • Cellular and Molecular Neuroscience

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  • Cite this

    Pasinetti, G. M., Osterburg, H. H., Kelly, A. B., Kohama, S., Morgan, D. G., Reinhard, J. F., Stellwagen, R. H., & Finch, C. E. (1992). Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for neuron aging. Molecular Brain Research, 13(1-2), 63-73. https://doi.org/10.1016/0169-328X(92)90045-D