Manipulating astrocyte support cells in the brain may offer a promising new way to treat Parkinson’s disease, research from University of Rochester shows.
The findings, using an animal model of the disease, reveal that a single therapy could concurrently repair multiple types of neurological damage caused by Parkinson’s, giving benefits that have not been seen in other methods.
“One of the central challenges in Parkinson’s disease is that many different cell types are damaged, each of which is of potential importance,” said lead author Chris Proschel, Ph.D. “However, while we know that the collective loss of these cells contributes to the symptoms of the disease, much of the current research is focused on the recovery of only one cell type.”
The progressive neurological disorder Parkinson’s disease affects an estimated one million Americans. It is linked with the loss of dopaminergic neurons. These are cells which produce the vital neurotransmitter dopamine.
Parkinson’s Far Ranging Impact
But Parkinson’s impact is in fact much more multifaceted and wide-ranging, disrupting basic signaling functions and triggering the destruction of several other types of cells found in the brain.
So even though preservation and restoration of dopaminergic neurons is key to slowing or reversing the course of the disease, it is increasingly clear that any successful long-term therapy must both protect the areas of the brain under attack and foster the repair of not only dopaminergic neurons but also the damage that occurs in other cell populations.
“Reversing the disease’s impact on the brain is akin to the challenges of fixing a house that is in the process of falling apart,” said Proschel. “If you only focus on addressing one aspect of the problem, such as the wiring, but ignore the fact that the roof is leaking and the foundation is crumbling, then you haven’t really carried out the necessary repairs and it is only a matter of time before the lights go out again.”
The research team isolated a human brain cell population found in the central nervous system called glial precursors. Carefully manipulating culture conditions and cell signals, they caused the precursor cells to produce a particular type of astrocytes.
Astrocytes usually get much less attention than their more glamorous relative the neuron. However, they are critical for sustaining a healthy environment in the brain. On the other hand, scientists are finding that astrocyte dysfunction can contribute to several neurological disorders.
Actualizing therapeutic implications of astrocyte research has proven to be difficult. The ability of labs such as Proschel’s to isolate and identify the unique properties of different kinds of astroctyes, essentially finding the right cell for the right job, offers the possibility of harnessing these cells for new therapies.
Astrocytes employed in the study differed from other types of astrocytes in a mature brain. When implanted into the brains of rats with Parkinson’s disease, the new cells acted like astrocytes found in the developing brain, which are more effective at building connections between nerves and creating a suitable environment for growth and repair.
As a result, the implanted astrocytes functioned like a repair kit, restoring health and stability to the structure and letting the brain’s nerve cells recover and restart normal activity.
Interneuron and Synaptophysin Recovery
The researchers were careful to implant the cells only after the rats had developed signs of Parkinson’s disease. This delay was important because it mimics how a similar therapy would be used in humans where the neurological damage caused by the disease precedes its visible symptoms.
The researchers saw that after transplantation, not only did dopaminergic neurons recover in the animals, but other nerve cells called interneurons were also rescued.
Interneurons play an important role in information processing and movement control, and are also lost in Parkinson’s disease. No previous therapies have treated these cells.
The astrocyte therapy also restored normal levels of synaptophysin, a protein that is essential for communication between nerve cells. The transplanted rats recovered motor skills to normal levels, essentially reversing the symptoms of the disease.
“The central importance of this work is in revealing a potentially new cell therapy, for which appropriate human cells are in hand, that can be used to restore multiple neuronal populations and to rescue the molecular machinery critical in communication between nerve cells even when cells are transplanted after the damage is already established,” said Mark Noble, Ph.D., a co-author of the study. “From what is already known about these cells, it seems likely that they offer a promising approach to a variety of neurological afflictions.”
C. Proschel, J. L. Stripay, C.-H. Shih, J. C. Munger, M. D. Noble.
Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons.
EMBO Molecular Medicine, 2014; DOI:10.1002/emmm.201302878
Image: Yirui Sun, Wellcome Images
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