Human evolution: your gut has a big brain (Introduction)

by David Turell , Tuesday, September 21, 2021, 18:45 (1169 days ago) @ David Turell

How glia exercise control:

https://medicalxpress.com/news/2021-09-gut-remarkable-role-intestinal-cells.html

"The Gulbransen lab studies enteric glial cells and how they regulate processes in the gut. "Lately researchers have noticed glia have active signaling roles—they talk to other glia, to neurons and to immune cells to regulate homeostasis, like a rheostat that turns neuron activity up or down," he explained.

"Hundreds of millions of neurons line the digestive tract to make the enteric nervous system. It has more neurons than the spinal cord, and the enteric glial cells surround each one. But for a long time, scientists were not excited about glia because they were not excitable cells—electrically speaking.

"'Once scientists could image other types of activity, they discovered the glia do exhibit forms of fast activity, just in different ways, through a type of firing mediated by calcium that allows them to signal to the neurons," said Gulbransen, who was just finishing a Ph.D. in neuroscience at the University Of Colorado Hospital in 2007 when new research suggested that glia not only communicated with other cells, but also expressed an antigen known as major histocompatibility complex class II, or MHC-II, in patients with Crohn's disease.

"'There are cells that present antigens such as MHC-II, and glia are one of them, but no one had studied their role in the immune system" Gulbransen explained. "Also, one of the major pathways and genes that are altered in IBD is MHC-II, and antigen presentation has been thought of as a dysfunctional mechanism in people with IBD."

"By comparing genetically modified mice incapable of expressing MHC-II on enteric glia to ones with fully functional expression of MHC-II, Aaron teased out the important function these molecules play. Presence of MHC-II antigens during inflammation triggered the signaling and activation of T- and B-cells that in turn activated immune cell subsets involved in anti-inflammatory mechanisms. Without MHC-II, the immune cells that reduce inflammation were much quieter.

"'The takeaway was that a dysfunction in T-cell activation means a person would have more activity towards more bacteria coming across the gut barrier and that drives more inflammation and tissue damage," Gulbransen said.

***

Like their unexpected ability to signal to other neurons through calcium instead of electricity, the researchers discovered that the glia also found an unexpected way to drive the expression of MHC-II and communicate with immune cells—autophagy, or the process of a cell eating components of itself. The glia sacrificed their own bodies to protect enteric neurons from inflammation.

"'That was really interesting because autophagy is a big pathway that is dysregulated in IBD," Gulbransen explained. "If these processes don't work very well, you lose the effective activation of tolerogenic immune cells and get overactivation of the immune system.'"

Comment: Studying a gut disease finds out how processes work employing glia. What I see is the amazing design involved in producing a precisely controlling brain for the gut.