Stimulation of non-α7 nicotinic receptors partially protects dopaminergic neurons from 1-methyl-4-phenylpyridinium-induced toxicity in culture
Section snippets
Materials
Dulbecco’s modified Eagle’s medium (DMEM), Hank’s balanced salt solutions (HBSS), trypsin–EDTA, fetal calf serum, and penicillin/streptomycin were purchased from Life Technologies (Rockville, MD, USA); normal goat serum, Vectastain ABC kit, and Vector VIP kit from Vector Laboratories (Burlingame, CA, USA); nicotine, d-tubocurarine, α-bungarotoxin, MPP+, poly-D-lysine and polyethyleneimine from Sigma Chemical (St. Louis, MO, USA); tyrosine hydroxylase (TH) antibody from Pel-Freez Biologicals
[3H]Epibatidine binding in culture
VM cells were grown in culture for up to 2 weeks. Specific [3H]epibatidine binding was observed in these cultures as early as 3 days after plating at which time cells had begun to extend processes and form a network. Binding increased with time in culture up to 7 days after plating and then plateaued until 10 days in culture (Fig. 1A). By 14 days in culture, binding had decreased to the level seen at day 3 and the cultures appeared less viable, although the results at this time point were very
Discussion
The present results show that nicotine partially protects against MPP+-induced toxicity in mesencephalic cultures. The degree of neuroprotection is similar to that observed in in vivo studies which demonstrate ∼20% protection against nigrostriatal degeneration after nicotine or cytisine administration (Janson et al., 1988a, Janson et al., 1988b, Fuxe et al., 1990, Janson et al., 1991, Janson and Moller, 1993, Ferger et al., 1998). The similarity in the magnitude of the protective effect against
Conclusion
The results show that stimulation of non-α7 nicotinic receptors partially protects dopaminergic mesencephalic neurons from MPP+-induced toxicity in culture. These results may suggest that nicotinic receptors represent a potential therapeutic target for delaying or preventing Parkinson’s disease. The symptoms of Parkinson’s disease do not manifest until nigrostriatal degeneration has progressed to about 70–80%; therefore, even a modest increase in the integrity of nigral dopaminergic neurons may
Acknowledgements
We thank Namitha Devendrarao for excellent technical assistance. This work was supported by the Tobacco Related Disease Research Program, #8RT-0105 and #7FT-0010.
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