Investigation of the therapeutic potential of N-acetyl cysteine and the tools used to define nigrostriatal degeneration in vivo.

摘要: The glutathione precursor N-acetyl-L-cysteine (NAC) is currently being tested on Parkinson's patients for its neuroprotective properties. Our studies have shown that NAC can elicit protection in glutathione-independent manners vitro. Thus, the goal of present study was to establish an animal model NAC-mediated which dissect underlying mechanism. Mice were infused intrastriatally with oxidative neurotoxicant 6-hydroxydopamine (6-OHDA; 4 μg) and administered intraperitoneally (100mg/kg). NAC-treated animals exhibited higher levels dopaminergic terminal marker tyrosine hydroxylase (TH) striatum 10d after 6-OHDA. As TH expression subject stress-induced modulation, we tracer FluoroGold into retrogradely label nigrostriatal projection neurons. expected, nigral staining cell counts FluoroGold(+) profiles both more sensitive measures degeneration than measurements relying alone. However, failed protect neurons 3 weeks following 6-OHDA, effect verified by four measures: striatal levels, TH(+) counts, levels. Some degree mild toxicity evident, suggesting caution must be exercised when as a neuron-counting tool designing experiments long-term delivery NAC--such clinical trials chronic disorders. Finally, strengths limitations tools used define are discussed.