Neuroprotective rather than neurorescue or neurorestorative effect of selegiline against MPTP-induced dopaminergic toxicity.
OBJECTIVE
To study the neuroprotective, neurorescue, neurorestorative effects of selegiline (Sel) on nigrostriatal dopaminergic neuronal system and its inhibition of brain monoamine oxidase B (MAO-B).


METHODS
The striatal levels of dopamine and its metabolites were measured using HPLC with electrochemical detection (HPLC-EC). The inhibition of MAO-B was tested by an improved fluorimetric assay.


RESULTS
1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) (30 mg.kg-1 i.p.) reduced the striatal dopamine level by 73% in mice. Selegiline (Sel, 10 mg.kg-1 i.p.) before, but not after, MPTP treatment protected against MPTP-induced nigrostriatal dopaminergic neurotoxicity. There were no differential effects between Sel and saline treatments on the recovery of striatal dopamine levels, which were partially restored during 2 wk. 1-Methyl-4-phenylpyridinium (MPP+) (5 mg.kg-1 i.p.) produced no dopaminergic neurotoxicity. Furthermore, Sel selectively and irreversibly inhibited mouse brain MAO-B in vitro (IC50 = 17 nmol.L-1, 95% confidence limits = 14-20 nmol.L-1).


CONCLUSIONS
Selegiline has neuroprotective rather than neurorescue or neurorestorative effects on MPTP-induced nigrostriatal dopaminergic neuronal degeneration, which is directly pertinent to its selective and irreversible inhibition of brain MAO-B activity.
Wu
W R
WR
Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Zhu
X Z
XZ
Guan
H J
HJ
Wang
R G
RG
Ji
X Q
XQ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D012642:Selegiline / Q000494:pharmacology*; D013997:Time Factors
D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D004298:Dopamine