Study Shows Brain Can Still Develop New Cells After 70 Years

A recent study is challenging a long-standing assumption regarding the adult brain. It surmises that individuals can continue to develop new brain cells into old age. Researchers at Sweden’s Karolinska Institutet, under Jonas Frisén’s leadership, have presented direct evidence that new neurons continue to develop in the memory center of the brain, the hippocampus, in 78-year-olds.

Brian Smith underscored the importance of this study, noting that it is fundamental to the ongoing debate in neuroscience related to whether or not neurogenesis (growing new neurons) ceases after childhood or continues throughout life.

The hippocampus is central to memory, learning, and mood, and is often called the "memory center" of the brain. Animal studies have revealed the continuous development of new neurons in this brain structure throughout life, yet researchers have had difficulty finding this in a human study.

In 2013, Frisén’s research team captivated the neuroscience field with what was a paradigm-shifting study. They used carbon-14 in DNA to date when human cells in the hippocampus were born and found evidence of new neurons developing in adult brains.

However, many scientists in the field were skeptical because they simply found dividing neural progenitor cells, which are foundational to the process of neurogenesis. In the present study, the research teams’ work focused on identifying definitive progenitor cells (cells that give rise to new neurons) in the human brain. Previously, no studies had looked for definitive progenitor cells in the human adult brain.

Through examining human brain samples, the authors were able to assess the installation of neurogenesis in humans from birth to adult ages of 78 years old. The human brain tissue was obtained from multiple biobanks in several different countries, a unique opportunity for researchers to study brain development across the human lifespan.

Researchers employed single-nucleus RNA sequencing, which analyzes gene activity in individual cell nuclei, often used to study brain development. Through this, they characterized all stages of progenitor cells in the human brain from stem cells to immature neurons. They also employed a mechanistic approach called flow cytometry, which allows the separation of the cells by characteristics, and then coupled this technique with machine learning to identify very small populations of dividing cells.

In brain tissue from children obtained during early childhood, the team was painstaking in confirming that all stages of neural progenitor cells were clearly identified. The principal finding of the study was the validation of definitive progenitor cells in the adult human brain. The researchers then demonstrated that these neural progenitor cells were actively dividing. They validated this by using antibodies to Ki67, a well-known marker of cell proliferation.

To identify the specific location of the new neurons within the brain of an adult, the authors utilized RNAscope and Xenium, which reveal sites of active gene expression in discrete locations of tissue.

Notably, in an important finding, the progenitor cells and young neurons were located in a small subregion of the hippocampus known as the dentate gyrus, which is a critical brain region that is involved with the formation of new memories, spatial learning, and adaptation to change.

The precise mapping of neural progenitor cells has added weight to the idea that the adult human brain continues to generate new neurons, while at the same time providing researchers with a specific region to investigate in future studies and prospective treatments.