Deficits in the activation and phosphorylation of hippocampal tyrosine hydroxylase in the aged Fischer 344 rat following intraventricular administration of 6-hydroxydopamine.
Tyrosine hydroxylase activity was measured under optimal and suboptimal assay conditions in hippocampal extracts from young (2 month), mature (12 month), and old (24 month) Fischer 344 male rats 72 h after the infusion of 200 micrograms of the neurotoxin 6-hydroxydopamine or vehicle into the lateral ventricle. The lesion resulted in a 45-55% decrease of tyrosine hydroxylase activity measured under optimal conditions (pH 6.1, 3.0 mM 6-methyl-5,6,7,8-tetrahydropterin) and an approximately 35% decrease in the relative concentration of immunoreactive tyrosine hydroxylase. When measured under suboptimal conditions (pH 6.6, 0.7 mM 6-methyl-5,6,7,8-tetrahydropterin), tyrosine hydroxylase activity in 2- and 12-month-old lesioned animals was twice that measured in vehicle-treated animals. However, in the old lesioned animals, tyrosine hydroxylase activity measured under suboptimal conditions was not different from that measured in age-matched vehicle-treated animals. Isoforms of tyrosine hydroxylase were identified on immunoblots after two-dimensional gel electrophoresis using enhanced chemiluminescence. The relative proportion of lower pI isoforms of tyrosine hydroxylase in the 2-month-old lesioned animals was greater than that observed in vehicle-treated controls. In contrast, no difference was seen in the relative proportion of tyrosine hydroxylase isoforms in the 24-month-old lesioned versus control animals. These data indicate that the ability of locus ceruleus neurons to rapidly respond to and compensate for insult is attenuated in 24-month-old Fischer 344 rats due to a deficit in stimulus-evoked enzyme phosphorylation.
Unnerstall
J R
JR
Department of Anatomy and Cell Biology, University of Illinois, Chicago College of Medicine 60612.
Ladner
A
A
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D004789:Enzyme Activation; D006624:Hippocampus / Q000201:enzymology* / Q000378:metabolism; D007276:Injections, Intraventricular; D007525:Isoelectric Focusing; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D011916:Rats, Inbred F344; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism* / Q000502:physiology
D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase