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Science News

Early Cellular Change in Parkinsonís Disease Neurons Detected

Scientists studying the development of Parkinson’s disease (PD) may have uncovered an early pathological marker of the disease. The research, published in the February 6 edition of Proceedings of the National Academy of Sciences, focused on a protein called alpha-synuclein.

Alpha-synuclein protein has been shown to be the main component of Lewy bodies, the large clumps of protein that build up in neurons and are a pathological hallmark of Parkinson’s. But how this protein works and what is its role in PD is still not well understood. 

Researchers wondered whether alpha-synuclein affected dopamine signaling, the process where dopamine travels one brain cell to another. Normal signaling allows normal movement. In PD, when cells can no longer carry out this signaling, movement is affected.

Researchers from Lund University in Sweden led by Anders Björklund, M.D., Ph.D., wanted to know whether alpha-synuclein had a role in disrupting the transmission of dopamine. The researchers engineered rats to mimic the symptoms of PD by injecting rats with a virus infected by alpha-synuclein. They then monitored the levels of dopamine outside the cells at several time points, as the rats began to develop PD pathology, to see whether there were problems with dopamine transmission. This allowed them to observe how alpha-synuclein disrupts dopamine transmission at different stages of PD development, even before symptoms are apparent.

Results

  • As quickly as 10 days after the animals began producing excess alpha-synuclein, there was subtle evidence of impaired dopamine signaling without the loss of brain cells.
  • Within three weeks, dopamine signaling was significantly impaired. Brain cells had not yet died; however, the cells began to become swollen and physically deformed—evidence of their ill health. 
  • Despite strong drops in dopamine and brain cell health, the body was able to use compensatory mechanisms to maintain normal movement.
  • By five weeks, normal behavior began to be slightly impaired much like at the early stage of PD.  Dopamine levels and neuronal health continued to drop. 
  • At later stages of measurement, all measures of dopamine transmission were impaired and cell death of dopamine neurons was widespread.  The animals demonstrated symptoms much like those of advanced PD.

What Does It Mean?

In Parkinson’s disease, dopamine-releasing brain cells slowly die. It has commonly been thought that the death of brain cells is the reason dopamine levels drop. What this study shows is that brain cells stop releasing dopamine as they become sick with excess alpha-synuclein. By identifying the role of alpha-synuclein in impairing dopamine release before cell death occurs, this study takes an important step in clarifying how PD progresses and the role of alpha-synuclein in that progression.

While this research took place in rats, causing their PD symptoms to appear at a greatly accelerated rate, it suggests several promising avenues for further research. First, it confirms recent speculation that brain cells lose their ability to function normally before they die. This gives hope to therapies that might restore the health of brain cells and potentially stop and dramatically reduce the symptoms of PD. Second, it suggests that therapies that target alpha-synuclein levels will be important in helping to restore normal dopamine transmission and brain cell health.  Third, by identifies biological changes that occur before brain cells die, which might help generate new ways of detecting PD before symptoms appear. 

Reference: Lundblad, M., Decressac, Mattsson, B, Bjorklund, A. (2012). Impaired neurotransmission caused by overexpression of α-synuclein in nigral dopamine neurons. Proceedings of the National Academy of Sciences, published ahead of print February 6, 2012, doi:10.1073/pnas.1200575109.

Source Date: Feb 29 2012