Intrinsic Antioxidant Properties of Dopaminergic Neurons


Kang, Un Jung, M.D.
University of Chicago, Chicago, IL

Abstract

Why do some dopaminergic (DA) neurons but not others fall prey to oxidative stress or mitochondrial disruption?  Either or both have been cited as cause for DA neuronal degeneration, and Dr. Un Jung Kang of the University of Chicago will use his continuing PDF funding to try to characterize these intrinsic properties of DA neurons.  Using rat tissue, Dr. Kang, who was also a Joint Junior Fellow (PDF/UPF), will attempt to elucidate why such selective degeneration exists in the parkinsonian brain and how it is affected by antiparkinson medications.

Progress Report (as of 8/2002)

Parkinson's disease (PD) is characterized by a relatively selective loss of dopamine neurons and this loss is attributed, at least in part, to oxidative stress. Therefore, one might assume that dopamine neurons are more susceptible to oxidative stress. However, we found that dopamine neurons grown in culture dishes can handle certain oxidative stresses better than other neurons. We hypothesized that normal dopamine neurons handle oxidative stress better than other neurons and that when this capacity to handle oxidative stress is disrupted, PD could develop. Therefore, the goal of this grant was to further understand the intrinsic properties of dopamine neurons that keep them safe from oxidative stresses in normal people. Specifically, we examined the role of an endogenous compound, tetrahydrobiopterin that is present at a high level in dopamine neurons. We showed that this compound lowers the levels of oxidative stress in many different neuronal and non-neuronal cells and could protect neurons from oxidative stress if they are provided with high levels of tetrahydrobiopterin. We also noted that normal dopamine neurons have high levels of glutathione, which is another endogenous antioxidant and is depleted in PD brains. This is consistent with the idea that normal dopamine neurons are equipped with enhanced defense against oxidative stress and depletion of such factors are associated with PD. Our studies provided an insight into the intrinsic antioxidant properties of dopamine neurons so that we may prevent the loss of or bolster such capacity as a measure to forestall the development of Parkinson's disease.