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Effects of R ‐ and S‐ apomorphine on MPTP‐induced nigro‐striatal dopamine neuronal loss
Author(s) -
Grünblatt Edna,
Mandel Silvia,
Maor Gila,
Youdim Moussa B. H.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00227.x
Subject(s) - mptp , apomorphine , chemistry , dopamine , neuroprotection , substantia nigra , tyrosine hydroxylase , agonist , monoamine oxidase b , monoamine oxidase , endocrinology , pharmacology , medicine , receptor , dopaminergic , biochemistry , biology , enzyme
In order to establish whether the antioxidant and iron‐chelating activities of R‐ apomorphine ( R‐ APO), a D 1 ‐D 2 receptor agonist, may contribute to its neuroprotective property, its S‐ isomer, which is not a dopamine agonist, was studied. The neuroprotective property of R ‐ and S‐ APO has been studied in the MPTP model of Parkinson's disease (PD). Both S‐ APO (0.5–1 mg/kg, subcutaneous) and R‐ APO (10 mg/kg) pretreatment of C57‐BL mice, protected against MPTP (24 mg/kg, intraperitoneally) induced dopamine (DA) depletion and reduction in tyrosine hydroxylase (TH) activity. However, only R‐ APO prevented nigro‐striatal neuronal cell degeneration, as indicated by the immunohistochemistry of TH positive neurones in substantia nigra and by western analysis of striatal TH content. R‐ APO prevented the reduction of striatal‐GSH and the increase in the ratio of GSSG over total glutathione, caused by MPTP treatment. In vitro both R‐ APO and S‐ APO inhibited monoamine oxidase A and B activity at relatively high concentrations (100 and 300 µmol/L, respectively). The elevated activity of TH induced by the two enantiomers may contribute to the maintenance of normal DA levels, suggesting that one of the targets of these molecules may involve upregulation of TH activity. It is suggested that the antioxidant and iron‐chelating properties, possible monoamine oxidase inhibitory actions, together with activation of DA receptors, may participate in the mechanism of neuroprotection by APO enantiomers against MPTP.