Difference in recovery patterns of striatal dopamine content, tyrosine hydroxylase activity and total biopterin content after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration: a comparison of young and older mice.
Striatal dopamine (DA) content, tyrosine hydroxylase (TH) activity, and total biopterin content were measured as parameters of recovery, after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in 7-week-old (young) and 28-week-old (older) C57 BL/6 mice. After 10 consecutive days of injection of MPTP (30 mg/kg/day) young mice were sacrificed at one day and 2, 4, 8, 12 and 20 weeks; older mice (20 mg/kg/day) at one day and 4, 8, and 12 weeks. All 3 parameters were markedly reduced one day after the last injection of MPTP. During the observation period, the parameters showed a gradual and partial recovery. The recovery rates of the 3 parameters differed significantly, especially during the early phases of 2-8 weeks. Total biopterin content showed a greater rate of recovery than TH activity and TH activity, a greater rate of recovery than DA content. In the older mice group, the recovery of all 3 parameters was retarded significantly, and dissociation of the recovery rates between the 3 parameters was more prominent. The results of our present study suggest that, following neurotoxic injury, the recovery of biopterin may play a significant role in dopaminergic terminal regeneration.
Nishi
K
K
Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
Kondo
T
T
Narabayashi
H
H
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001708:Biopterins / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000494:pharmacology; D011725:Pyridines / Q000633:toxicity*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D009498:Neurotoxins; D011725:Pyridines; D001708:Biopterins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine