New research suggests that the adult brain can regenerate neurons that integrate into motor circuits, potentially aiding in the repair of damaged neural networks in Huntington’s and other diseases. Dr. Abdellatif Benraiss, a senior author of the study published in Cell Reports, highlighted the significance of this discovery. “Our research shows that we can encourage the brain’s own cells to grow new neurons that join in naturally with the circuits controlling movement,” he said. “This discovery offers a potential new way to restore brain function and slow the progression of these diseases.” Benraiss is a research associate professor at the University of Rochester Medical Center’s Center for Translational Neuromedicine, led by Dr. Steve Goldman.
It was once believed the adult brain couldn’t generate new neurons, but it is now known that progenitor cells in brain niches can produce new neurons. These cells primarily produce neurons in early development and switch to glial cells shortly after birth. In the ventricular zone, located near the striatum, a brain region severely affected by Huntington’s disease, these cells are found to congregate.
Research in Goldman’s lab demonstrated that delivering BDNF and Noggin proteins to progenitor cells in mice could stimulate neuron generation. These new neurons migrated to the striatum, developing into medium spiny neurons, which are the primary cells lost in Huntington’s. This induction of neuron formation was noted in both mice and primates.
The integration of these new neurons into brain networks was previously unclear. In a mouse model of Huntington’s, the research showed that the neurons connect with motor control networks, replacing lost neuron functions. Using genetic tagging, researchers followed the new cells over time. “In this paper, we used a combination of electrophysiology, optogenetics, and mouse behavior to show that these cells are not only produced in the adult brain but functionally restore motor circuits in both healthy mice and in the context of Huntington’s disease,” noted Jose Cano, PhD, a lead author of the study.
Through optogenetics, researchers mapped connections between new neurons and other brain regions, confirming their integration into motor control networks.
The study points to a potential treatment strategy for Huntington’s disease by stimulating the brain to replace lost neurons and restore communication pathways. “Taken together with the persistence of these progenitor cells in the adult primate brain, these findings suggest the potential for this regenerative approach as a treatment strategy in Huntington’s and other disorders characterized by the loss of neurons in the striatum,” said Benraiss.
The authors propose combining this approach with other cell replacement therapies. Goldman’s lab has shown glial cells called astrocytes significantly influence Huntington’s disease. Correcting dysfunctional astrocytes with healthy ones has shown promise in slowing disease progression in mice. These glial replacement therapies are under preclinical development.
