Chronic lesions differentially decrease tyrosine hydroxylase messenger RNA in dopaminergic neurons of the substantia nigra.
Long-term effects of lesions were analyzed in terms of gene expression. Nine months after unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (s. nigra), the remaining dopaminergic (DAergic) neurons (tyrosine hydroxylase (TH) cells determined by immunocytochemistry (ICC] on the lesioned side were atrophic with smaller nucleoli. By in situ hybridization, the DAergic neurons on the lesioned side had a 50% smaller TH-mRNA concentration than on the contralateral non-lesioned side. However, beta-tubulin mRNA concentration in DAergic neurons was unaffected by the lesion. The lesions did not alter TH-mRNA concentration in the contralateral non-lesioned side by comparison with unoperated controls. We propose that chronic lesions have long-term effects on gene expression because of damage sustained during compensatory hyperactivity after the lesion, or because of decreased trophic support from other neurons.
Pasinetti
G M
GM
Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Lerner
S P
SP
Johnson
S A
SA
Morgan
D G
DG
Telford
N A
NA
Finch
C E
CE
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation; D006892:Hydroxydopamines; D008297:Male; D009693:Nucleic Acid Hybridization; D016627:Oxidopamine; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D006892:Hydroxydopamines; D012333:RNA, Messenger; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine