Understanding the Role of Cerebrospinal Fluid in Brain Aging

This text is part of the special booklet Living fully

The brain is like the computer of the human body. And if we can simply replace electronic computers when they age and fail, this is not the case with the human brain. Hence the importance of fully understanding how aging works.

This is the task undertaken by two professors from the University of Sherbrooke, Benoit Laurent, from the Department of Biochemistry and Functional Genomics, and Marc-Antoine Lauzon, from the Department of Chemical Engineering and Biotechnology Engineering. Both are associated with the Center for Research on Aging of the CIUSSS de l’Estrie – CHUS.

“The research we are undertaking focuses on the factors that lead to the aging of brain cells,” explains Benoit Laurent. In particular, we study a part of the brain called the choroid plexus, whose function is to secrete cerebrospinal fluid. »

The cerebrospinal fluid, in which the brain is bathed, has two main functions: it is through it that the proteins capable of controlling the differentiation of stem cells arrive, namely the mechanism that allows human beings to renew their present cells in the brain and thus cause neurogenesis; and it serves to eliminate waste and toxins produced by the brain. “Our hypothesis, continues Benoit Laurent, is that the cerebrospinal fluid, by its quantity and quality, plays a decisive role in the aging of the brain. »

Culture of human cells

The catch is that it’s difficult, if not impossible, to do biochemical research on human brain cells. live. Instead, laboratory animals are used, which has its limits. This is where Marc-Antoine Lauzon and his organoids come into play. The culture of human cells in the laboratory, using a Petri dish, is not new, but over the past twenty years, researchers in biochemistry and biotechnological engineering have developed a method that allows the culture of three-dimensional human cells, i.e. capable of clumping together.

“Our laboratory has bioreactors which, using stem cells, can cultivate these cell agglomerations,” explains Marc-Antoine Lauzon. First, a cocktail of different molecules, proteins, hormones and nutrients is administered to promote cell growth. In a second step, we serve a second cocktail which, in turn, causes the differentiation of stem cells. The latter can then mimic certain functions of human organs, hence the name organoids. »

In the case that concerns the two researchers, these are organoids that mimic the functioning of the choroid plexus, and therefore specifically the secretion of cerebrospinal fluid. This is the perfect scientific tool for studying the functioning of brain cells and their aging.

What’s more, the stem cells used are induced pluripotent stem cells, that is to say differentiated cells from living people which are genetically programmed to become stem cells again. “The advantage with this type of stem cells, continues Marc-Antoine Lauzon, is that they retain a genetic fingerprint of the donor. Thus, it is possible for us with cells from a 20 or 70 year old person to cultivate organoids reproducing the conditions of a 20 or 70 year old person. »

The purpose of the research

The research conducted by Professors Laurent and Lauzon is in its infancy, since funding materialized last fall. “In a first step, specifies Benoit Laurent, we are going to use the organoids of the choroid plexus to compare its functioning at different ages, which should allow us to better understand the aging process of brain cells and the role of cerebrospinal fluid. Does it change over time and how does it change? In a second step, we hope to be able to improve the functioning of the cerebrospinal fluid by discovering therapeutic means. »

However, a caveat is in order. “We are not looking to stop the aging of the brain, specifies Marc-Antoine Lauzon, our research is not the quest for the fountain of youth. Benoit Laurent continues: “Humans will continue to age as well as their brains, it is a natural and inevitable process. On the other hand, it may be possible to age better. »

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