Examining Cofilin-1 Expression within the Substantia Nigra in Parkinson's Disease

Parkinson’s disease (PD) is a neurological condition that affects the motor movement of an individual, impacting the ability to move or speak. Approximately 60,000 Americans are diagnosed with the disease each year, yet after 200 years from the first publication on PD the pathogenesis of the disease is still a mystery. However, the disease has been characterized by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. Degeneration of these neurons results in a reduction of dopamine, a neurotransmitter that relays messages to the basal ganglia for coordinated movement. Despite the fact that the mechanism of neurodegeneration has not been defined, growing evidence suggests oxidative stress is the main defective neuronal pathway contributing to the neuron’s loss of function. In oxidative stress, reactive oxygen species damage the mitochondria and lead to a reduction in ATP synthesis. Following a reduction in ATP levels, the cytoskeletal protein cofilin-1 aggregates with F-actin, leading to the formation of rods within neurons. The cofilin-actin rods have the potential to interrupt normal neuronal function that may contribute to the degeneration of dopaminergic cells. Another defining hallmark of PD are neurons containing abnormal protein aggregates known as Lewy bodies. Lewy bodies, comprising predominantly of α-synuclein, are proposed to be a method of removing dysfunctional proteins from interfering with normal cell functions. The objective of this study was to localize the expression of cofilin-1 and examine whether aberrant expression of cofilin-1 is present in post-mortem brain tissue of patients with PD. Cofilin-1 expression was examined within dopaminergic neurons and Lewy bodies by dual-labeling immunofluorescence. The primary antibody concentrations were first optimized using immunohistochemistry staining with 3, 3'-diaminobenzidine and were found to be 1:100 for tyrosine hydroxylase (dopaminergic marker) and 1:2000 α-synuclein (Lewy body marker). The results showed that Cofilin-1 was present within the axons of dopaminergic neurons and Lewy bodies. This is the first characterization of the deposition of Cofilin-1 in Lewy bodies in PD. The results provide a link between aberrant Cofilin-1 expression and PD-pathology.