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Neurotransmitters Envisaged as Controllers of Stem Cell Activity

Adult, or somatic, stem cells support surrounding tissues by delivering a supply of daughter somatic cells, ready to replace those lost over time. This stem cell activity declines with age, and in the best studied stem cell populations this appears to be more a matter of signaling than a matter of inherent dysfunction. Stem cells react to rising levels of damage in tissues, or rather to the changes in signaling that result from that damage. Old stem cells put into a young environment perform as well as their younger counterparts. This decline with age may have evolved to limit cancer risk, but it brings the certainty of a slow decline into organ failure.

Many research groups are searching for the signals responsible for adjusting stem cell activity. The scientists here demonstrate that the autonomic nervous system makes important contributions to this signaling environment, and thus specific neurotransmitters may be a useful target for therapies to suppress or enhance stem cell function in various contexts. When it comes to aging, the function of the autonomic nervous system is known to change in later life, but more work is needed to solidify how this new research fits in to the bigger picture.

Somatic stem cells are microscopic workhorses, constantly regenerating cells throughout the body: skin and the lining of the intestine, for example. Researchers have demonstrated for the first time that stem cell proliferation is directly controlled by the autonomic nervous system (ANS). The ANS controls all of our unconscious functions: breathing, blood flow, digestion, and so forth. Its two major networks of nerve fibers run from the brain through the entire body, with neurons reaching into nearly every organ. These neurons release chemicals called neurotransmitters, which can affect target cells directly or indirectly.

When neurotransmitters bind to receptors in the membranes of certain cells, they elicit a direct response within the cell. But changes in cells can also occur when neurotransmitters induce a general state of inflammation or alter blood flow, an indirect route of action for the ANS. Scientists had suspected the ANS was involved in stem cell proliferation, but they didn't know if the relationship was direct or indirect. A direct relationship could have greater implications for drug interventions to treat medical conditions. "If you wanted to change the regeneration potential of an organ, for example, you wouldn't have to stimulate or suppress the activity of those neurons. Instead, you could just figure out what neurotransmitters are controlling proliferation and then get that chemical to those stem cells with targeted drug delivery."

To demonstrate that stem cell behavior was changing as a result of ANS stimulation, the researchers grew intestinal epithelial cells in the lab and exposed them to high levels of two neurotransmitters, norepinephrine and acetylcholine. Norepinephrine is a major neurotransmitter of the sympathetic nervous system, or "fight or flight" branch of the ANS, while acetylcholine is produced by the parasympathetic nervous system, or "rest and digest" branch. When the researchers simulated activation of either of those systems, they saw a decrease in stem cell proliferation. This suggests the body may avoid putting energy into making new cells when the fight or flight system is active.

Link: https://www.eurekalert.org/pub_releases/2018-10/uoic-isf101718.php

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