Slow changes of tyrosine hydroxylase gene expression in dopaminergic brain neurons after neurotoxin lesioning: a model for neuron aging.
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.
Pasinetti
G M
GM
Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Osterburg
H H
HH
Kelly
A B
AB
Kohama
S
S
Morgan
D G
DG
Reinhard
J F
JF
Stellwagen
R H
RH
Finch
C E
CE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D016627:Oxidopamine / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012689:Sequence Homology, Nucleic Acid; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D015306:Biogenic Monoamines; D012333:RNA, Messenger; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid