Protection from oxidation enhances the survival of cultured mesencephalic neurons.
Oxidative stress has been linked to the destruction of dopaminergic neurons in the substantia nigra and may be a significant factor in both Parkinson's disease and MPTP toxicity. Using primary cultures of embryonic rat mesencephalon and standard immunocytochemical techniques, we have examined the survival of tyrosine hydroxylase-containing (TH+) neurons cultured in the presence of antioxidants and/or in an environment of low oxygen partial pressure. The number of TH+ neurons increased approximately twofold if superoxide dismutase, glutathione peroxidase (GP), or N-acetyl cysteine (NAC) were added to the culture media. Exposure of the neurons to a 5% oxygen environment (38 torr, i.e., 38 mm Hg) also increased the survival of TH+ neurons by about twofold. A dramatic enhancement of survival, however, was seen when NAC was used in combination with the 5% oxygen environment. In this case, the number of TH+ neurons increased fourfold from nontreated controls. Morphological changes were also noted. GP increased the average neurite length while NAC increased the average area of the cell body in the TH+ neuron. These results suggest that manipulation of oxidative conditions by changing the ambient O2 tension or the level of antioxidants promotes survival of TH+ neurons in culture and may have implications for transplantation therapies in Parkinson's disease.
Colton
C A
CA
Department of Physiology and Biophysics, Georgetown University Medical School, Washington, DC 20007, USA.
Pagan
F
F
Snell
J
J
Colton
J S
JS
Cummins
A
A
Gilbert
D L
DL
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005979:Glutathione Peroxidase / Q000494:pharmacology*; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D014446:Tyrosine 3-Monooxygenase; D013482:Superoxide Dismutase; D010100:Oxygen; D000111:Acetylcysteine