Researchers mobilize brain's native stem cells to replenish neuron lost in Huntington's disease

Published on June 7, 2013 at 8:24 AM · No Comments

Researchers have been able to mobilize the brain's native stem cells to replenish a type of neuron lost in Huntington's disease. In the study, which appears today in the journal Cell Stem Cell, the scientists were able to both trigger the production of new neurons in mice with the disease and show that the new cells successfully integrated into the brain's existing neural networks, dramatically extending the survival of the treated mice.

"This study demonstrates the feasibility of a completely new concept to treat Huntington's disease, by recruiting the brain's endogenous neural stem cells to regenerate cells lost to the disease," said University of Rochester Medical Center (URMC) neurologist Steve Goldman, M.D., Ph.D., co-director of Rochester's Center for Translational Neuromedicine.

Huntington's disease is an inherited neurodegenerative disease characterized by the loss of a specific cell type called the medium spiny neuron, a cell that is critical to motor control. The disease, which affects some 30,000 people in the U.S., results in involuntary movements, problems with coordination, and, ultimately, in cognitive decline and depression. There is currently no way to slow or modify this fatal disease.

For Goldman, the idea behind his strategy to treat the disease emerged from his decades-long study of neural plasticity in canaries. Songbirds like canaries have intrigued biologists because of their ability - unique in the animal kingdom - to lay down new neurons in the adult brain. This process, called adult neurogenesis, was first discovered by Goldman and Fernando Nottebohm of the Rockefeller University in the early 1980s, when the two realized that when learning new songs new neurons were added to regions of the bird's brain responsible for vocal control.

"Our work with canaries essentially provided us with the information we needed to understand how to add new neurons to adult brain tissue," said Goldman. "Once we mastered how this happened in birds, we set about how to replicate the process in the adult mammalian brain."

Humans already possess the ability to create new neurons. Goldman's lab demonstrated in the 1990s that a font of neuronal precursor cells exist in the lining of the ventricles, structures found in the core of the human brain. In early development, these cells are actively producing neurons. However, shortly after birth the neural stem cells stop generating neurons and instead produce glia, a family of support cells that pervade the central nervous system. Some parts of the human brain continue to produce neurons into adulthood, the most prominent example is the hippocampus where memories are formed and stored. But in the striatum, the region of the brain that is devastated by Huntington's disease, this capability is "switched off" in adulthood.

Goldman and his team spent the past decade attempting to unravel the precise chemical signaling responsible for instructing neural stem cells when to create neurons and when to create glia cells. One of the most critical clues came directly from the earlier research with canaries. In the part of the bird's brain were new songs are acquired and neurons added, the scientists observed the regulated expression of a protein called brain derived neurotrophic factor, or BDNF. When the production of this protein is triggered, the local neural stem cells are instructed to produce neurons.

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