Show that neurodegenerative diseases attack brain stem cells and prevent them from generating healthy neurons

An international team led by researchers from the Superior Council for Scientific Research (CSIC) verified that neurodegenerative diseases attack the brain stem cells and prevent the generation of new neurons.

The study, published in the journal Science and which was presented at a press conference at the CSIC headquarters (Madrid), demonstrates for the first time the existence of stem cells in the hippocampus, a region of the adult human brain. Its proliferation allows the generation of new neurons throughout life, a process known as adult hippocampal neurogenesis.

“We already knew that neurogenesis took place in the brain of rodents, but this is the first time that the existence of these stem cells in the human brain has been demonstrated”, emphasizes the director of the study. Maria Llorens-Martin, researcher at the Severo Ochoa Molecular Biology Center (CBMSO), a joint center of the CSIC and the Autonomous University of Madrid.

“The biggest challenge of this work was to obtain a collection of samples suitable for the visualization of these cells. This took us 11 years”, explains the expert to SINC during a press conference held this Thursday.

The results obtained deepen the knowledge of the human brain and will make it possible to lay the foundations for the future development of therapeutic and regenerative tools that slow down the advance of neurodegenerative diseases.

This research also reveals that the adult hippocampal neurogenesis process is severely impaired in patients with amyotrophic lateral sclerosis (OA), Huntington’s Disease, Parkinson’s, Lewy body dementia, and frontotemporal dementia. “These neurodegenerative diseases specifically attack stem cells, which prevents the generation of new healthy neurons”, emphasizes the specialist.

Likewise, each of these diseases generates its own cellular ‘signature’, more markedly damaging certain cellular subpopulations that are part of the adult hippocampal neurogenesis process.

A specialized cellular niche

In the adult brain, the generation of new neurons from stem cells is possible thanks to the existence of a specialized cell niche ─hippocampal neurogenic niche─ present in very few regions of the brain, including the hippocampus. This has a complex structure formed by glial cells and blood vessels.

This study shows that changes in the aforementioned generation of neurons are closely related to the functioning of the hippocampal cell niche in our species.

“Thanks to our work, we know that this niche creates the ideal permissive environment for new neurons to mature and survive, and that it becomes a hostile environment during physiological and pathological aging”, details the author.

The existence and cellular composition of this niche in humans was unknown until now. This work shows that both the adult neurogenesis process itself and the cell niche in which new neurons are generated undergo changes throughout life.

“In particular, we found that the functioning of the cells of microglia, a type of immune system cell responsible for regulating the number and maturation of new neurons that are generated in the hippocampus, suffers damage in elderly people”, says the expert.

All of this makes the adult hippocampal neurogenesis process decrease over aging, although it occurs up to 90-100 years, as demonstrated by previous research by the same scientific team.

The advantage of neural plasticity

The birth of new neurons in the hippocampus confers great remodeling and adaptation capacity to the mammalian brain, a concept called neural plasticity. However, the hippocampus is also highly vulnerable to neurodegenerative and psychiatric diseases, in which some cell populations are more susceptible to certain diseases than others.

“In patients with ALS, Huntington or Parkinson, we see an increase in the number of mature neurons as well as stem cells. However, this does not mean that there is an increased rate of neurogenesis. There is also more cell death and less stem cell activity. In other words, although the process initially seems to be increased, it ends up failing and the new neurons do not acquire a correct maturation”, emphasizes the author.

In all these neurodegenerative diseases, a reduction in the proliferative activity of stem cells and an increase in their quiescence (a vegetative state, without cell division).

Furthermore, the newly generated neurons had important defects in their maturation, as they were not able to complete it properly and acquired aberrant morphologies.

“In patients with neurodegenerative diseases, the new neurons do not acquire a correct morphology, as they have several extensions and their orientation is totally different from healthy people. Therefore, these neurons are not able to connect correctly with the rest of the circuit”, concludes the researcher.

Rights: Creative Commons.