Aging of the dopaminergic system and motor behavior in mice intoxicated with the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication of mice is a standard model of Parkinson's disease (PD). However, it does not reproduce functionally PD. Given the occurrence of PD during aging, symptoms might only be detected in MPTP-intoxicated mice after aging. To address this, mice injected with MPTP at 2.5 months were followed up to a maximum age of 21 months. There was no loss of dopamine cells with aging in control mice; moreover, the initial post-MPTP intoxication decrease in dopamine cell was no longer significant at 21 months. With aging, striatal dopamine level remained constant, but concentrations of the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were markedly reduced in both groups. There was also a late impairment of fine motor skills. After MPTP intoxication, hyperactivity was immediately detected and it became greater than in control mice from 14 months of age; fine motor skills were also more impaired; both these symptoms were correlated with striatal dopamine, DOPAC and HVA concentrations. In bothgroups, neither motor symptoms nor dopamine changes worsened with age. These findings do not support the notion that PD develops with age in mice after MPTP intoxication and that the motor deficits seen are because of an aging process.
AP-HP, Hôpital Charles Foix, Unité d'Explorations Fonctionnelles, Ivry-sur-Seine, France. sophie.schumm@cfx.aphp.fr
Sophie
S
Schumm
Claude
C
Sebban
Charles
C
Cohen-Salmon
Jacques
J
Callebert
Jean-Marie
JM
Launay
Jean-Louis
JL
Golmard
Lydie
L
Boussicault
Isabelle
I
Petropoulos
Audrey
A
Hild
Estelle
E
Rousselet
Annick
A
Prigent
Bertrand
B
Friguet
Jean
J
Mariani
Etienne C
EC
Hirsch
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000375:Aging / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D045442:Rotarod Performance Test; D013223:Statistics as Topic; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid