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Gut bacteria may play a role in regulating myelination in the brain's prefrontal cortex
      10/26/15 03:04 PM

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Microbe-free mice have hypermyelination of the prefrontal cortex

author name
by Kristina Fiore
Staff Writer, MedPage Today

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
Note that this mouse study found increased myelination in certain brain areas when gut microbiota were eradicated.

CHICAGO -- Gut bacteria may play a role in regulating myelination in the prefrontal cortex (PFC), researchers reported here.

Microbe-free mice had greater expression of myelin-related genes and hypermyelination in the PFC compared with control animals, Alan Hoban, PhD, of University College Cork in Ireland, and colleagues presented at a poster session at the Society for Neuroscience meeting here.

"These animals have no microbiota, so it could be that a lack of signals from the gut aren't check-pointing oligodendrocytes, since we saw with the hypermyelinated fibers was they had so many more wraps of myelin," Hoban told MedPage Today. "That means the oligodendrocytes may be excessively turning, and whatever is missing from the gut signaling to the brain is not telling them to stop -- but that's a very broad interpretation," he cautioned.

The past decade has brought an influx of research on the role of microbiota in gut-brain interactions, including mounting evidence that mood can be impacted by the intestinal flora. But other work has also suggested that gut bugs could play a role in conditions such as autism spectrum disorder (ASD), Parkinson's, and even demyelinating disorders of the central nervous system, including multiple sclerosis.

"MS is an autoimmune disease, so we were interested in how the microbiota may be driving this," Hoban told MedPage Today.

He and his colleagues conducted genome-wide RNA sequencing in the PFC of control mice, microbe-free mice, and mice that were previously microbe-free but were re-colonized.

They conducted RNA sequencing to evaluate differential gene expression, and then validated that data with qRT-PCR. They also conducted transmission electron microscopy in order to quantify myelin thickness relative to axonal diameter, known as the g-ratio. And finally, they did Western blot analysis to assess the expression of proteins from myelin component genes in the PFC.

Overall, they found that microbe-free mice had increased myelin gene expression, but only in the PFC -- not in five other brain regions including the cerebellum, hippocampus, amygdala, striatum, and frontal cortex.

"We examined a lot of different regions ... and we found that it was solely the PFC that displayed an increase in myelin gene expression," Hoban said.

Expression of myelinating genes was not heightened in any brain regions in control animals, nor in mice that had their microbiota restored, which suggests that myelin processing problems could be repaired, the researchers said.

Hoban and the paper's senior author John Cryan, PhD, also of University College Cork, noted that the hypermyelination seen in animals without gut bacteria "tells us the microbiome provides a break on myelination."

Indeed, the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis cannot be induced in microbe-free mice, Cryan said.

In addition to the gene expression patterns, the researchers conducted transmission electron microscopy and saw greater myelination of axons, as measured by a higher lamina number and greater myelin diameter.

The findings were also confirmed on Western blot, which revealed a greater expression of proteins from myelin component genes in the PFC in microbe-free animals.

Cryan said the next steps are trying to figure out the mechanisms behind the relationship between gut bacteria and myelination in the PFC.

"What could be driving these changes, and why is it specific to the PFC?" Cryan said. "We need to see what signals the microbiome is sending. We need to look at metabolites, at the vagus nerve and the other connections, and see whether we can recapitulate it with certain strategies or certain bacterial strains."

"We know that colonization of the entire microbiome has an effect, but what if we wanted to put back a single bacteria" to impact myelin regulation, he added.

Cryan noted that the concept of the microbiome having an influence on neurologic and psychiatric processes is relatively new and may still have its critics, but "we're slowly beginning to find that all of the fundamental processes of brain function are somehow being regulated by the microbiome."

"These findings encourage a multidisciplinary approach" to understanding disease processes for conditions like multiple sclerosis in order to develop better therapies, Cryan said.

Hoban disclosed no financial relationships with industry.

Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
This report is part of a 12-month Curriculum In Context series.

last updated 10.26.2015

Primary Source
Society for Neuroscience
Source Reference: Hoban AE, et al "Regulation of myelination in the prefrontal cortex by the microbiota" SFN 2015; Abstract 162.08.

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