The Role of Iron and Oxidative Stress in Parkinsons Disease
Speaker: Sathya Ravichandran
Abstract: Parkinsons Disease (PD) is an age-related neurodegenerative disease, which results in the loss of control over muscle movement, and eventually renders the afflicted person unable to perform the most trivial tasks. PD is a syndrome with many apparent endpoints that are not completely characterized. However, oxidative stress appears to be a common component of the etiology of the disease. Iron has been observed to be a catalyst for reactions that produce reactive oxygen species, which may cause extensive damage to membranes, proteins and DNA in vitro. Thus oxidative stress in PD may result from an abnormal accumulation of iron. It has been observed that in patients with PD iron accumulates in the astrocytes (supporting cells of the brain that surround neurons) but not in the neurons. However, there is a substantial loss in the number of nigral striatal neurons, which are responsible for the production of a neurotransmitter that is secreted during sensory and motor nerve transmissions. Thus I hypothesize that oxidative stress occurs in non-neuronal cells but causes neuronal death.
My project will test this hypothesis. The experimental system that will be used is a coculture model where astrocytes are overlaid with Pheochromocytoma (PC) 12 cells, a neuron-like cell line. An iron overload will be induced in the astrocytes by cysteamine addition to cause iron accumulation identical to that seen in PD. Experimentally, oxidant production in the astrocytes and PC 12 cells as well as the oxidative damage in PC 12 cells will be monitored with a concentration-dependent iron accumulation. Finally, experiments will be set up to define whether lipoic acid (a potent antioxidant and iron chelator) addition can prevent oxidative damage and neuronal loss.
Over the summer, as part of the Howard Hughes Medical Institute Undergraduate Research Fellowship Program, the PC 12 cells were characterized with respect to parameters of oxidant production, oxidative damage, antioxidant status and mitochondrial membrane potential. Primary astrocytes from the brains of young rats were also isolated and are in the process of being cultured for characterization experiments and the coculture model.