They manage to rejuvenate neurons through cellular reprogramming.

An investigation conducted by researchers from CIBER area of ​​neurodegenerative diseases (CIBERNED) And University of Barcelona describes how mice brain neurons can rejuvenate yourself through a cycle of cellular reprogramming controlled, which helps restore some of the altered neurological properties and functions.

A study published in the journal ‘Cell Stem cell‘ may open new perspectives for studying neurodegenerative diseases in patients. From an innovative perspective, he examines the process of cellular rejuvenation in neurons and highlights the role of so-called Yamanaka factors, key proteins for reversing aging that are still poorly understood in the nervous system.

Researchers recall that with age, a neuron loses synaptic connections with other neurons, loses the ability to transmit nerve impulses, and its metabolism also changes. This process of neuronal aging, inevitable over time, is especially accelerated and becomes risk factor for neurodegenerative pathologies like Alzheimer’s disease.

The research is carried out by experts Daniel del Toro and Albert Giralt from the Faculty of Medicine and Health Sciences, Institute of Neuroscience (UBneuro) and the Center for Production and Testing of Advanced Therapies (CREATIO) UB, IDIBAPS and CIBERNED, as well as Rüdiger Klein from the Max Planck Institute for Biology. Intelligence (Germany). The work, whose first co-author is Sofia Saballa (UB-IDIBAPS-CIBERNED), also featured prominently by expert Manuel Serrano from the Barcelona IRB.

Yamanaka Factors

In 2012, a Japanese scientist Shinya Yamanaka and the Briton John Gurdon received Nobel Prize in Medicine for research to reprogram differentiated cells and return them to a state typical of pluripotent cells. Those known as Yamanaka factors, namely Oct4, Sox2, Klf4 and c-Myc, are transcription factors present throughout the scientific literature on cellular reprogramming.

Although much of the international research has focused on the rejuvenation and regeneration of peripheral tissues (skin, muscle, liver and heart), new work is now delving into the effects they can cause in the central nervous system. 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 UB Department of Biomedicine, emphasizes that “when Yamanaka factors are introduced during the development phase, more neurons are generated and the brain becomes larger (he can do twice as much). This translates to better motor and social activity in adulthood“.

“These results 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 discover that if we control the expression of these factors very precisely, we can also control the process of cell proliferation and get a brain with a larger cerebral cortex without losing proper structure and function,” he adds. .

For his part, Professor Albert Giralt clarifies that in the case of adult mice, “the expression of Yamanaka factors in adult neurons causes These cells rejuvenate and protect 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 neuron rejuvenation process. 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.

Cell reprogramming

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 growth of aberrant cell populations, that is, tumors.

Experts detail that through research and through precise control in specific neural populations, 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.

Likewise, they highlight that “since beneficial effects have also been identified when factors occur very early in brain development, we believe it would be interesting study its consequences in neurodevelopmental disorders“.

First of all, they have an epigenetic effect, and this will affect 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.