Relative to most organs, the brain has very limited regenerative potential. But within it, a population of immature cells persists in adulthood, suggesting that it, too, possesses an innate ability to repair itself. These cells are termed neural stem cells and are considered immature because they have not fulfilled their developmental options; instead, they have maintained their ability to proliferate, and have kept open their options to mature into any one of the main cell types of the brain (neurons, astrocytes, or oligodendrocytes).

In mammals, adult neural stem cells were first discovered in two small areas of the rodent brain, the subventricular zone, and the dentate gyrus of the hippocampus. In these areas, neural stem cells are able to proliferate and some of the new cells mature to become neurons. This may be a mechanism to provide new neurons throughout the lifespan of the animal in areas that are involved with olfaction, learning, and memory [all experience-based processes with a need to register information].

But we recently showed that in the adult brain and spinal cord, neural stem cells are plentiful and widespread. We address the question of their function to understand how they can be coaxed to help in disease. To do so, we study the mechanisms that regulate stem cell survival and proliferation, and as a consequence, their numbers. We have discovered that these cells use biochemical pathways in distinct ways than most mature cell types in the body, and we have found pharmacological means to regulate their numbers. This has provided a tool to study their role in the context of neurodegenerative diseases such as Parkinson’s disease, and brain insults such as ischemic stroke.

We found that a variety of treatments that increase the numbers of these cells result in the dramatic rescue of neurons that would otherwise die due to disease. We think this is because neural stem cells physically associate with neurons and produce factors that support their survival. Our results show that great benefits can be achieved by targeting the endogenous population of neural stem cells, and encouraging them to protect injured neurons. We are investigating how these mechanisms may be applied to other degenerative disorders like Amyotrophic Lateral Sclerosis (also known as Lou Gehrig’s disease).

Our efforts are focused on uncovering additional facets of the signals that regulate neural stem cells in order to devise new treatments, including ones that can be used clinically. This requires basic research into the mechanisms that control stem cell survival and proliferation. For example, we recently showed that cholera toxin, which regulates a number of cellular functions also regulates the biochemical pathways we previously discovered and greatly increases stem cell numbers in culture. We then apply our findings in models of degenerative disease. We aim to develop therapeutic strategies that stop the degeneration of tissues and not merely treat symptoms.