UB Researchers Rejuvenate Brain Neurons Through Cellular Reprogramming: More Neurons, More Brain Plasticity – News

Specifically, the team studied the effects of controlled expression of Yamanaka factors in mouse brains during cycles of cellular reprogramming at different stages of neuronal development.

Daniel del Toro, principal investigator of the Ramón y Cajal program at the Department of Biomedicine at UB, emphasizes that “when Yamanaka factors are introduced during development, more neurons are generated and the brain becomes more voluminous (it can reach twice the size). “This leads to improved motor and social functioning in adulthood.” “These results,” the expert continues, “are explained by the fact that we have made all brain cells capable of expressing these factors, including stem cells.” “It was very surprising to find that if we very precisely control the expression of these factors, we can also control the process of cell proliferation and produce brains with a larger cortex without losing proper structure and function,” he adds.

The researcher admits that “we were also surprised to see that from a behavioral perspective there were no negative behavioral consequences, and the mice even showed improved motor behavior and social interaction.”

For his part, Professor Albert Giralt clarified that in the case of adult mice, “the expression of Yamanaka factors in adult neurons causes these cells to rejuvenate and exhibit protection against neurodegenerative diseases such as Alzheimer’s disease.” “In this case, we induced the expression of Yamanaka factors only in mature neurons. Because these cells do not divide, their number does not increase, but we have identified many markers indicating the process of neuronal rejuvenation. In these rejuvenated neurons, we find that the number of synaptic connections increases, the altered metabolism is stabilized, and the epigenetic profile of the cell is normalized,” details Giralt. “This whole set of changes has a very positive effect on their functionality as neurons,” the expert says.

Reprogramming Cells to Fight Neurodegenerative Diseases

Understanding the aging process at the cellular scale opens new horizons in the fight against disease through cellular reprogramming. However, this process also carries the risk of causing the growth of aberrant cell populations, that is, tumors.

Experts clarify that “in our research and through precise control in specific neural populations, we have ensured that these factors are not only safe, but also improve neuronal synaptic plasticity, as well as higher order cognitive functions, such as the ability to socialize and form new ones.” memories. In addition, they emphasize that “since beneficial effects have also been identified when factors occur at very early stages of brain development, we believe it would be interesting to study their consequences in neurodevelopmental disorders.”

So how do these factors affect the nervous system? All indications are that Yamanaka factors operate at at least three molecular levels. Firstly, they have an epigenetic effect and influence gene transcription (DNA methylation process, histones, etc.). It will also compromise metabolic pathways and mitochondrial function (production and regulation of cellular energy). Finally, they can affect many genes and signaling pathways involved in synaptic plasticity.

Work published in the journal Cell Stem cellexpands knowledge of the functions of the Yamanaka factors described so far. These factors are known to improve regeneration after damage to retinal ganglion cells (David A. Sinclair, Harvard University, 2020) and also induce epigenetic changes in dentate gyrus neurons of the mouse hippocampus (Jesus Avila, CBMSO-CSIC-UAM, and Manuel Serrano , IRB Barcelona, ​​2020). The researchers conclude that based on the new findings, “we want to encourage future research to determine which other nervous system diseases may benefit from cell reprogramming technology, delve into the underlying molecular mechanisms to develop new therapeutic strategies, and ultimately benefit” . The results are close to clinical practice in treating patients.

Help Article:

Shen, Yi-Ru; Zaballa, Sofia, etc..“Expanding the neocortex and protecting against neurodegeneration with in natural conditions transient reprogramming. Cell Stem cellOctober 2024 DOI:10.1016/j.stem.2024.09.013