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Summary: Researchers discover gut microbes may influence microRNA in the prefrontal cortex and amygdala, two areas of the brain associated with depression and anxiety.

Source: BioMed Central.

Research published in the open access journal Microbiome sheds new light on how gut bacteria may influence anxiety-like behaviors. Investigating the link between gut bacteria and biological molecules called microRNAs (miRNAs) in the brain; researchers at the APC Microbiome Institute at University College Cork, which is funded by Science Foundation Ireland, found that a significant number of miRNAs were changed in the brains of microbe-free mice. These mice are reared in a germ-free bubble and typically display abnormal anxiety, deficits in sociability and cognition, and increased depressive-like behaviors.

Dr Gerard Clarke, the corresponding author said: “Gut microbes seem to influence miRNAs in the amygdala and the prefrontal cortex. This is important because these miRNAs may affect physiological processes that are fundamental to the functioning of the central nervous system and in brain regions, such as the amygdala and prefrontal cortex, which are heavily implicated in anxiety and depression.”

miRNAs are short sequences of nucleotides (the building blocks of DNA and RNA), which can act to control how genes are expressed. miRNA dysregulation or dysfunction is believed to be an underlying factor contributing to stress-related psychiatric disorders, neurodegenerative diseases and neurodevelopmental abnormalities. miRNA changes in the brain have been implicated in anxiety-like behaviors.

Dr Clarke said: “It may be possible to modulate miRNAs in the brain for the treatment of psychiatric disorders but research in this area has faced several challenges, for example, finding safe and biologically stable compounds that are able to cross the blood-brain barrier and then act at the desired location in the brain. Our study suggests that some of the hurdles that stand in the way of exploiting the therapeutic potential of miRNAs could be cleared by instead targeting the gut microbiome.”

The researchers found that levels of 103 miRNAs were different in the amygdala and 31 in the prefrontal cortex of mice reared without gut bacteria (GF mice) compared to conventional mice. Adding back the gut microbiome later in life normalized some of the changes to miRNAs in the brain.

The findings suggest that a healthy microbiome is necessary for appropriate regulation of miRNAs in these brain regions. Previous research demonstrated that manipulation of the gut microbiome affects anxiety-like behaviors but this is the first time that the gut microbiome has been linked to miRNAs in both the amygdala and prefrontal cortex, according to the authors.

The researchers used next-generation-sequencing (NGS) to find out which miRNAs were present in the amygdala and the prefrontal cortex of groups of 10-12 control mice with a normal gut microbiota, GF mice and ex-GF mice — which had been colonized with bacteria by housing them with the control mice — and adult rats whose normal microbiota had been depleted with antibiotics.

They found that depleting the microbiota of adult rats with antibiotics impacted some miRNAs in the brain in a similar way to the GF mice. This suggests that even if a healthy microbiota is present in early life, subsequent changes in adulthood can impact miRNAs in the brain relevant to anxiety-like behaviors, according to the authors.

The authors note that the exact mechanism by which the gut microbiota is able to influence the miRNAs in the brain remains unclear. Even though the study shows that effects of the microbiota on miRNAs are present in more than one species (mice and rats), further research into the possible connection between gut bacteria, miRNAs and anxiety-like behaviors is needed before the findings can be translated to a clinical setting.

Dr Clarke said: “This is early stage research but the possibility of achieving the desired impact on miRNAs in specific brain regions by targeting the gut microbiota — for example by using psychobiotics — is an appealing prospect.”

Source: BioMed Central
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Microbial regulation of microRNA expression in the amygdala and prefrontal cortex” by Alan E. Hoban, Roman M. Stilling, Gerard M. Moloney, Rachel D. Moloney, Fergus Shanahan, Timothy G. Dinan, John F. Cryan and Gerard Clarke in Microbiome. Published online August 25 2017 doi:10.1186/s40168-017-0321-3

Abstract

Microbial regulation of microRNA expression in the amygdala and prefrontal cortex

Background
There is growing evidence for a role of the gut microbiome in shaping behaviour relevant to many psychiatric and neurological disorders. Preclinical studies using germ-free (GF) animals have been essential in contributing to our current understanding of the potential importance of the host microbiome for neurodevelopment and behaviour. In particular, it has been repeatedly demonstrated that manipulation of the gut microbiome modulates anxiety-like behaviours. The neural circuits that underlie anxiety- and fear-related behaviours are complex and heavily depend on functional communication between the amygdala and prefrontal cortex (PFC). Previously, we have shown that the transcriptional networks within the amygdala and PFC of GF mice are altered. MicroRNAs (miRNAs) act through translational repression to control gene translation and have also been implicated in anxiety-like behaviours. However, it is unknown whether these features of host post-transcriptional machinery are also recruited by the gut microbiome to exert control over CNS transcriptional networks.

Results
We conducted Illumina® next-generation sequencing (NGS) in the amygdala and PFC of conventional, GF and germ-free colonized mice (exGF). We found a large proportion of miRNAs to be dysregulated in GF animals in both brain regions (103 in the amygdala and 31 in the PFC). Additionally, colonization of GF mice normalized some of the noted alterations. Next, we used a complementary approach to GF by manipulating the adult rat microbiome with an antibiotic cocktail to deplete the gut microbiota and found that this strategy also impacted the expression of relevant miRNAs.

Conclusion
These results suggest that the microbiome is necessary for appropriate regulation of miRNA expression in brain regions implicated in anxiety-like behaviours.

“Microbial regulation of microRNA expression in the amygdala and prefrontal cortex” by Alan E. Hoban, Roman M. Stilling, Gerard M. Moloney, Rachel D. Moloney, Fergus Shanahan, Timothy G. Dinan, John F. Cryan and Gerard Clarke in Microbiome. Published online August 25 2017 doi:10.1186/s40168-017-0321-3

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Summary: Researchers report children who underwent general anesthesia and surgery prior to the age of one showed decreased white matter volume and integrity.

Source: University of Iowa.

Researchers say white matter integrity, volume may be decreased.

General anesthesia and surgery in otherwise healthy infants under the age of 1 year old could be associated with decreases in the amount of white matter in the brain, as well as reductions in the remaining white matter’s integrity, according to a new University of Iowa Health Care study published this week in the Online First edition of Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists.

Researchers conducted structural magnetic resonance imaging (MRI) tests on 34 children between the ages of 12 and 15 years old – 17 otherwise healthy patients who had been administered general anesthesia and had surgery in their first year of life, and 17 control subjects who had not had surgery or general anesthesia before their first birthday.

What they found was that the volume and integrity of white matter – the tissue that connects different regions of gray matter from one part of the brain to another – was on average 1.5 percentage points lower in patients who had undergone surgery involving general anesthesia as infants.

“The most rigorous previous study in humans looked at the effects of general anesthesia during infancy on cognitive functions of 2-year-olds, and results showed no effect,” says Robert Block, PhD, associate professor of anesthesia at the UI Carver College of Medicine and first author on the study. “This study is looking specifically at the white matter structure and how it is affected.”

Prior studies of anesthesia examining brain structure mostly involved animals, Block says. He says this is the first study in relatively healthy humans to measure amounts and integrity of white matter in different parts of the brain.

The Food and Drug Administration (FDA) issued warnings in April advising that lengthy or multiple uses of general anesthesia and sedation in children under the age of 3 could affect the development of children’s brains.

“The FDA may have jumped the gun a little in their warning because they based it mostly on animal studies,” Block says. The topic needs a lot more research specifically examining human brain development.”

The UI study was funded through a small grant from SmartTots – a multi-year collaboration between the FDA and the International Anesthesia Research Society designed to examine the safety of anesthetic and sedative drugs being administered to young children. Block says he’d like to repeat and expand the study with a larger group of patients, because “in general, the bigger the sample size, the more convincing the study and the results.”

Block says investigators aren’t yet sure of the significance of a 1.5 percentage point difference in white matter volume.

“There is the question of whether this is functionally significant, and we don’t yet have the answer to that,” he says. “That’s one reason we need to look at a larger group.”

Additional UI researchers involved in the study include Vincent Magnotta, PhD; Emine Bayman, PhD, James Choi, MD, Joss Thomas, MD, and Karolie Kimble, RN,BA.

Funding: Funding was provided by SmartTots.

Source: Molly Rossiter – University of Iowa
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: The study will appear in Anesthesiology.

Connie comments: Use mother’s massage and breastmilk to help the infant thrive.

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