Regrowing dopaminergic neurons may lead to new therapy for Parkinson's disease

Boise State UniversityFeb 16 2016

While scientists are unsure of the molecular causes of Parkinson's Disease, they do know the disorder's tremors and other motor dysfunctions are linked to a loss of dopaminergic neurons located in the substantia nigra, a structure in the midbrain.

Dopaminergic neurons are our main source of dopamine, which is responsible for emotional response and plays an important role in movement. For many years, their loss has been viewed as irreversible.

But a new paper by Brad Morrison's research group in the Department of Biological Sciences at Boise State University suggests the possibility of regrowth of dopaminergic neurons in adult mammals. Co-authors are Joshua Albright, Iva Stojkovska, Abir Rahman and Connor Brown.

Their results, published in the journal Neuroscience Letters (http://www.sciencedirect.com/science/article/pii/S0304394016300180), also show that the rate of replenishment for these neurons is similar to the rate of loss observed in an inflammatory response mouse model of Parkinson's Disease. This may indicate that inflammatory insult inhibits the natural generation of neurons leading to Parkinson's Disease.

This is significant because Parkinson's disease is the most common motor disorder and the second most prevalent neurodegenerative disease. Current medications treat only symptoms and after time lose effectiveness. Learning how to regenerate these neurons could offer potential avenues for preventing neuronal loss and better inform stem cell transplantation efforts.

Morrison hypothesized that cells could regenerate in adults but were somehow being blocked in Parkinson's Disease, explaining progression of the disease. This goes against current dogma, which posits that only a handful of neuronal populations are able to regenerate in adult mammalian brains.

Taking a novel approach, he devised a system to genetically trace the lineage of dopaminergic neurons from stem cells. After removing the gene from stem cells using recombinant DNA technology, he then waited six months. At the end of that time, he saw that removal of the gene affected mature dopaminergic neurons, implying that they must be replenished by stem cells.

He now is characterizing the stem cells responsible for this process as well as looking at the potential correlation of inflammation and a reduction in dopaminergic neurons.