TUESDAY, 12 JULY 2016 / PUBLISHED IN BLOG

Introduction to Brain Plasticity and Aging

The human brain, as it turns out, is far more malleable than we once thought, even adult brains. However, they are subject to age-related diseases and disorders, such as dementia and diminished cognitive function. There is hope that medical science may be able to replace brain cells and restore memory in aging patients thanks to new discoveries in neural stem cell techniques.

New Techniques in Neural Stem Cell Research

Researchers at the Texas A&M Health Science Center College of Medicine recently published new findings in the journal Stem Cells Translational Medicine. These findings suggest a new technique for preparing donor neural stem cells and grafting them into an aged brain can regenerate tissue that has succumbed to structural, chemical, and functional changes, as well as a host of neurocognitive changes that can be attributed to aging.

Key Findings from the Study

The study, titled “Grafted Subventricular Zone Neural Stem Cells Display Robust Engraftment and Similar Differentiation Properties and Form New Neurogenic Niches in the Young and Aged Hippocampus,” was led by Ashok K. Shetty, Ph.D., a professor in the Department of Molecular and Cellular Medicine. Shetty is also the associate director of the Institute for Regenerative Medicine and a research career scientist at the Central Texas Veterans Health Care System.

Focus on the Aged Hippocampus

Shetty and his team at Texas A&M focus on the aged hippocampus, which plays an important role in making new memories and connecting them to emotions. They took healthy donor neural stem cells and implanted them into the hippocampus of an animal model, enabling them to regenerate tissue.

Significance of the Hippocampus

“We chose the hippocampus because it’s so important in learning, memory, and mood function,” Shetty said. “We’re interested in understanding aging in the brain, especially in the hippocampus, which seems particularly vulnerable to age-related changes.” The volume of this part of the brain decreases during the aging process, potentially related to a decline in neurogenesis (production of new neurons) and memory deficits.

Challenges in the Aged Hippocampus

The aged hippocampus exhibits signs of age-related degenerative changes, such as chronic low-grade inflammation and increased reactive oxygen species. Bharathi Hattiangady, assistant professor at the Texas A&M College of Medicine and co-first author of the study, was excited to discover that the aged hippocampus can accept grafted neural stem cells as well as the young hippocampus does, a discovery with significant implications for treating age-related neurodegenerative disorders.

Neural Stem Cell Grafting Process

In this new study, the team found that neural stem cells engrafted well onto the hippocampus in both young and older animal models. Not only did these implanted cells survive, but they also divided several times to create new cells. “They had at least three divisions after transplantation,” Shetty said. “The total yield of graft-derived neurons and glia was much higher than the number of implanted cells, in both the young and aged hippocampus.”

Creation of New Neural Stem Cell Niches

In both old and young brains, a small percentage of the grafted cells retained their stemness feature—an essential characteristic of a stem cell that distinguishes it from ordinary cells—and continuously produced new neurons. This process creates a new ‘niche’ of neural stem cells, which continue to produce new neurons at least three months after implantation.

Comparison to Previous Efforts

Past efforts to rejuvenate brains using fetal neurons were not as successful. Immature cells, such as neural stem cells, can tolerate the hypoxia (lack of oxygen) and trauma of the brain grafting procedure better than relatively mature neurons. The research team used a new technique of preparing the donor neural stem cells, leading to these promising results.

The Role of Brain Marrow

The researchers used donor cells from the sub-ventricular zone of the brain, an area called the “brain marrow,” analogous to bone marrow. This area holds a number of neural stem cells that persist throughout life, continuously producing new neurons that migrate to the olfactory system and respond to injury signals.

Potential of Induced Pluripotent Cells from Skin

Even a small stem cell sample can be expanded in culture, making the procedure minimally invasive. In the future, a single skin cell might suffice to create induced pluripotent stem cells, which can be pushed into neural stem cells. This eliminates the need to obtain cells from the brain, potentially revolutionizing the process.

Future Research Directions

Although the success of the grafted cells is promising, further research is needed to determine if the increased grey matter improves cognition. “Next, we want to test the impact of the implanted cells on behavior and determine if implanting neural stem cells can reverse age-related learning and memory deficits,” Shetty said. He is focused on rejuvenating the aged brain to promote successful aging, maintaining normal cognitive function, and the ability to make memories.