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 greater than 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3,4-Dihydroxyphenylacetic Acid / metabolism
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Aging
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Amino Acid Sequence
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Animals
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Biogenic Monoamines / metabolism*
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Corpus Striatum / drug effects
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Corpus Striatum / growth & development
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Corpus Striatum / metabolism*
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Dopamine / metabolism
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Gene Expression Regulation, Enzymologic* / drug effects
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Homovanillic Acid / metabolism
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Humans
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Hydroxyindoleacetic Acid / metabolism
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Immunohistochemistry
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Male
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Molecular Sequence Data
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Neurons / drug effects
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Neurons / enzymology
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Neurons / physiology*
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Norepinephrine / metabolism
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Nucleic Acid Hybridization
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Oxidopamine / pharmacology*
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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RNA, Messenger / metabolism*
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Rats
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Rats, Inbred F344
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Sequence Homology, Nucleic Acid
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Serotonin / metabolism
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Substantia Nigra / drug effects
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Substantia Nigra / growth & development
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Substantia Nigra / metabolism*
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Tyrosine 3-Monooxygenase / genetics*
Substances
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Biogenic Monoamines
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RNA, Messenger
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3,4-Dihydroxyphenylacetic Acid
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Serotonin
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Hydroxyindoleacetic Acid
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Oxidopamine
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Tyrosine 3-Monooxygenase
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Dopamine
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Norepinephrine
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Homovanillic Acid