TY - JOUR
T1 - Neuroprotective effect of riluzole in MPTP-treated mice
AU - Araki, Tsutomu
AU - Kumagai, Toshihiko
AU - Tanaka, Katsuyuki
AU - Matsubara, Mitsunobu
AU - Kato, Hiroyuki
AU - Itoyama, Yasuto
AU - Imai, Yutaka
N1 - Funding Information:
This study was supported, in part, by a Grant-in-Aid for Scientific Research (C) 13670627 from the Japan Society for the Promotion of Science.
PY - 2001/11/9
Y1 - 2001/11/9
N2 - The neuroprotective effects of riluzole, a Na+ channel blocker with antiglutamatergic activity, and MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, were compared in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in mice. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (10 mg/kg) at 1 h intervals and then the brains were analyzed 1, 3 and 7 days after the treatment. Dopamine and DOPAC levels were significantly decreased in the striatum from 1 day after MPTP treatment. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatment. Riluzole antagonized the MPTP-induced decrease in dopamine, DOPAC and HVA levels in the striatum. On the other hand, MK-801 prevented the MPTP-induced decrease in DOPAC levels, but not in dopamine levels in the striatum. An immunohistochemical study indicated that riluzole can protect against MPTP-induced neuronal damage in the substantia nigra. These results suggest that riluzole is effective against MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.
AB - The neuroprotective effects of riluzole, a Na+ channel blocker with antiglutamatergic activity, and MK-801, a blocker of N-methyl-D-aspartate (NMDA) receptors, were compared in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in mice. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (10 mg/kg) at 1 h intervals and then the brains were analyzed 1, 3 and 7 days after the treatment. Dopamine and DOPAC levels were significantly decreased in the striatum from 1 day after MPTP treatment. A severe depletion in dopamine and DOPAC levels was found in the striatum 3 and 7 days after MPTP treatment. Riluzole antagonized the MPTP-induced decrease in dopamine, DOPAC and HVA levels in the striatum. On the other hand, MK-801 prevented the MPTP-induced decrease in DOPAC levels, but not in dopamine levels in the striatum. An immunohistochemical study indicated that riluzole can protect against MPTP-induced neuronal damage in the substantia nigra. These results suggest that riluzole is effective against MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway.
KW - Dopamine
KW - Immunohistochemistry
KW - MK-801
KW - MPTP
KW - Mice
KW - Parkinson's disease
KW - Riluzole
KW - Striatum
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U2 - 10.1016/S0006-8993(01)02944-4
DO - 10.1016/S0006-8993(01)02944-4
M3 - Article
C2 - 11684056
AN - SCOPUS:0035834342
VL - 918
SP - 176
EP - 181
JO - Molecular Brain Research
JF - Molecular Brain Research
SN - 0006-8993
IS - 1-2
ER -