Title

 

Authors

G. Calia¹, V. Mazzarello¹, S. Dedola², G. Bazzu², R. Migheli², P.A. Serra², M.S. Desole², Rocchitta G.^2
 
1Dept. of Biomedical Sciences, Medical School, University of Sassari, Italy
²Dept. of Neuroscience, Medical School, University of Sassari, Italy

 

Abstract

Parkinson’s disease (PD) is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine (DA) (Kim et al., 2002); consequently, the functioning of the nigro-striatal dopaminergic system is impaired. Parkinsonian symptoms are relieved by administration of L-dihydroxyphenylalanine (L-DOPA), which is converted by neuronal aromatic L-aminoacid decarboxylase into DA. Dopaminergic neurons, however, continue to die despite the L-DOPA treatment (Basma et al., 1995). Oxidative stress is widely believed an important pathogenetic mechanism of neuronal death in Parkinson's disease (Halliwell, 1992), although it is still not clear whether it is an initial event causing cell death or a consequence of the disease. L-DOPA can undergo auto-oxidation (Serra et al., 2000) to generate quinones and reactive oxygen species (ROS), which would further load the pre-existing condition of oxidative stress at nigro-striatal sites (Basma et al., 1995). Death of nigral dopaminergic neurons in PD has been reported to occur by apoptosis: DA and L-DOPA have been shown to induce oxidative stress-mediated apoptosis in cultured neuronal cells (Desole et al., 1997). The subventricular zone (SVZ) in mammalian brain contains adult neural stem cells (aNSC) that have the potential to produce new neurons, astrocytes and oligodendrocytes. We deemed of interest the study of the fate of L-DOPA (50µM) and DA (50µM) added to the stem cell culture. The extracellular concentration of L-DOPA and DA were quantified by HPLC. Mediumcontaining stem cells protected the L-Dopa and DA from complete autoxidation and their final concentrations, after 72h, was, respectively, 60% and 20% of the initial values while the same medium without stem cells led to a rapid and total autoxidation of L-Dopa and DA during the first 24h. The latter data is consistent with the ability of stem cells to protect DA and L-DOPA from autoxidation. This antioxidant power may be of revelance to the use of aNSC to afford neuroprotection in animal models of PD.
 
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