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New Insights into Neuron Regeneration in the Adult Brain
Recent research has revealed that the adult brain has the capability to generate new neurons that can integrate into critical motor circuits. This discovery indicates that by leveraging natural brain processes, it may be possible to repair damaged neural networks in conditions such as Huntington’s disease and similar disorders.
“Our findings suggest that we can stimulate the brain’s inherent cells to develop new neurons that seamlessly integrate into the circuits that control movement,” explained Abdellatif Benraiss, PhD, a key researcher involved in the study published in the journal Cell Reports. “This breakthrough presents a promising avenue for restoring brain functionality and potentially decelerating the progression of various neurological diseases.” Dr. Benraiss is affiliated with the lab of Steve Goldman, MD, PhD, at the University of Rochester Medical Center (URMC).
Understanding Adult Neurogenesis
The notion that new neurons could emerge from the adult brain was once dismissed. However, it is now recognized that specific brain regions harbor progenitor cells capable of generating new neurons. While these cells predominantly produce neurons during early life, they largely transition to the generation of glial cells shortly after birth. A key region for these progenitor cells is the ventricular zone, which lies adjacent to the striatum—a brain area severely affected by Huntington’s disease.
The concept of adult neurogenesis was first highlighted by Goldman and colleagues in the 1980s, stemming from studies on neuroplasticity in canaries. Notably, songbirds exhibit unique abilities to form new neurons corresponding with their learning of new songs. These investigations helped identify various proteins, including brain-derived neurotrophic factor (BDNF), which instruct progenitor cells to grow into neurons.
Goldman’s lab further established that introducing BDNF alongside Noggin to progenitor cells in rodent brains led to the formation of new neurons. These cells migrated into the striatum, where they developed into medium spiny neurons, which are primarily lost in Huntington’s disease. Moreover, Benraiss and Goldman confirmed that similar approaches could stimulate new neuron formation in primate subjects.
Integrating New Neurons into Brain Networks
Despite promising advances, the degree of integration of these newly formed medium spiny neurons into existing brain networks was not well understood. The recent research involving a mouse model of Huntington’s disease clarified that these neurons not only developed but also effectively linked with the motor control circuits already in place, thereby compensating for the lost neuronal functions due to Huntington’s.
Using a genetic tagging technique, researchers traced the development of new neurons and their integration over time. “In our study, we employed a combination of electrophysiology, optogenetics, and behavioral assessments to demonstrate that these neurons are produced in the adult brain and can repair motor circuits, both in healthy conditions and within the context of Huntington’s disease,” remarked Jose Cano, PhD, a postdoctoral associate in Goldman’s lab and the lead author of the study.
The advanced methodologies allowed the team to map connections between newly formed neurons and adjacent cells, as well as other brain regions. By utilizing optogenetics, the researchers could turn these new cells on and off, corroborating their incorporation into larger networks that are pivotal for motor control.
Therapeutic Implications for Huntington’s Disease
The findings from this study suggest a viable therapeutic avenue for Huntington’s disease, emphasizing the potential of encouraging the brain to replace lost neurons with newly formed, functional counterparts. “These results, paired with the sustained presence of progenitor cells in the adult primate brain, highlight the regenerative potential of this strategy for treating Huntington’s and other neuron-loss-related disorders,” noted Benraiss.
The researchers advocate that this regenerative approach could be enhanced by combining it with other cell replacement therapies. Earlier studies in Goldman’s laboratory indicated that glial cells, specifically astrocytes, play a crucial role in the pathology of Huntington’s disease, as their dysfunction contributes to neuronal impairment. Interventions aiming to replace unhealthy glial cells with their healthy counterparts have shown promise in decelerating disease progression in mouse models. Currently, these therapies are undergoing preclinical development.
Co-authors of the research include Cathryn Mangiamele and Maiken Nedergaard from URMC. Goldman and Nedergaard are also associated with the University of Copenhagen. Financial support for the study was provided by CNS2, Inc., the Huntington Disease Golf Classic, and the Hereditary Disease Foundation.
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