Biochemical alterations of the striatum in an MPTP-treated mouse model of Parkinson's disease.
We investigated the biochemical alterations of the striatum of mice subjected to seven experimental schedules with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treatment. The mice were treated intraperitoneally (i.p.) with MPTP (20 mg/kg in saline) four times a day at 2-hr intervals showed severe and persistent depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, as compared with those (1) treated with MPTP (15 mg/kg in saline, i.p.) once a day for 14 consecutive days; (2)MPTP (30 mg/kg in saline, i.p.) twice a day for 5 consecutive days; (3) MPTP (10 mg/kg in saline, i.p.) four times a day at 1-hr intervals for 2 consecutive days; (4) MPTP (20 mg/kg in saline, i.p.) once a day for 4 consecutive days; (5) MPTP (20 mg/kg in saline, i.p.) twice a day for 2 consecutive days; (6) MPTP (20 mg/kg in saline, i.p.) twice a day for 4 consecutive days. In our Western blot analysis, furthermore, the mice that received MPTP (20 mg/kg in saline) four times a day at 2-hr intervals showed a severe decrease of the striatal tyrosine hydroxylase (TH) protein levels and a significant increase of the striatal glial fibrillary acidic protein (GFAP) levels. These results demonstrate that the model with acute MPTP treatment can cause severe neuronal damage in the mouse striatum, as compared to the model with continuous treatment with MPTP. Thus our findings may support the validity of acute MPTP treatment model for unraveling in the neurodegenerative processes in PD.
Kuroiwa
Hayato
H
Department of Neurobiology and Therapeutics, The University of Tokushima, Tokushima, 770-8505, Japan.
Yokoyama
Hironori
H
Kimoto
Hiroki
H
Kato
Hiroyuki
H
Araki
Tsutomu
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage* / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D003342:Corpus Striatum / Q000201:enzymology / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000494:pharmacology; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; 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