Posted on 09/22/2017 2:08:53 AM PDT by Enchante
Mothers who experience an infection severe enough to require hospitalization during pregnancy are at higher risk of having a child with autism. Two new studies from MIT and the University of Massachusetts Medical School shed more light on this phenomenon and identify possible approaches to preventing it.
In research on mice, the researchers found that the composition of bacterial populations in the mother’s digestive tract can influence whether maternal infection leads to autistic-like behaviors in offspring. They also discovered the specific brain changes that produce these behaviors.
“We identified a very discrete brain region that seems to be modulating all the behaviors associated with this particular model of neurodevelopmental disorder,” says Gloria Choi, the Samuel A. Goldblith Career Development Assistant Professor of Brain and Cognitive Sciences and a member of MIT’s McGovern Institute for Brain Research. If further validated in human studies, the findings could offer a possible way to reduce the risk of autism, which would involve blocking the function of certain strains of bacteria found in the maternal gut, the researchers say. Choi and Jun Huh, formerly an assistant professor at UMass Medical School who is now a faculty member at Harvard Medical School, are the senior authors of both papers, which appear in Nature on Sept. 13. MIT postdoc Yeong Shin Yim is the first author of one paper, and UMass Medical School visiting scholars Sangdoo Kim and Hyunju Kim are the lead authors of the other.
Reversing symptoms
A 2010 study that included all children born in Denmark between 1980 and 2005 found that severe viral infections during the first trimester of pregnancy translated to a threefold risk for autism, and serious bacterial infections during the second trimester were linked with a 1.42-fold increase in risk. These infections included influenza, viral gastroenteritis, and severe urinary tract infections.
Similar effects have been described in mouse models of maternal inflammation, and in a 2016 Science paper, Choi and Huh found that a type of immune cells known as Th17 cells, and their effector molecule, called IL-17, are responsible for this effect in mice. IL-17 then interacts with receptors found on brain cells in the developing fetus, leading to irregularities that the researchers call “patches” in certain parts of the cortex.
In one of the new papers, the researchers set out to learn more about these patches and to determine if they were responsible for the behavioral abnormalities seen in those mice, which include repetitive behavior and impaired sociability.
The researchers found that the patches are most common in a part of the brain known as S1DZ. Part of the somatosensory cortex, this region is believed to be responsible for proprioception, or sensing where the body is in space. In these patches, populations of cells called interneurons, which express a protein called parvalbumin, are reduced. Interneurons are responsible for controlling the balance of excitation and inhibition in the brain, and the researchers found that the changes they found in the cortical patches were associated with overexcitement in S1DZ.
When the researchers restored normal levels of brain activity in this area, they were able to reverse the behavioral abnormalities. They were also able to induce the behaviors in otherwise normal mice by overstimulating neurons in S1DZ.
The researchers also discovered that S1DZ sends messages to two other brain regions: the temporal association area of the cortex and the striatum. When the researchers inhibited the neurons connected to the temporal association area, they were able to reverse the sociability deficits. When they inhibited the neurons connected to the striatum, they were able to halt the repetitive behaviors.
Microbial factors
In the second Nature paper, the researchers delved into some of the additional factors that influence whether or not a severe infection leads to autism. Not all mothers who experience severe infection end up having child with autism, and similarly not all the mice in the maternal inflammation model develop behavioral abnormalities. “This suggests that inflammation during pregnancy is just one of the factors. It needs to work with additional factors to lead all the way to that outcome,” Choi says. A key clue was that when immune systems in some of the pregnant mice were stimulated, they began producing IL-17 within a day. “Normally it takes three to five days, because IL-17 is produced by specialized immune cells and they require time to differentiate,” Huh says. “We thought that perhaps this cytokine is being produced not from differentiating immune cells, but rather from pre-existing immune cells.”
Previous studies in mice and humans have found populations of Th17 cells in the intestines of healthy individuals. These cells, which help to protect the host from harmful microbes, are thought to be produced after exposure to particular types of harmless bacteria that associate with the epithelium.
The researchers found that only the offspring of mice with one specific type of harmless bacteria, known as segmented filamentous bacteria, had behavioral abnormalities and cortical patches. When the researchers killed those bacteria with antibiotics, the mice produced normal offspring.
“This data strongly suggests that perhaps certain mothers who happen to carry these types of Th17 cell-inducing bacteria in their gut may be susceptible to this inflammation-induced condition,” Huh says. Humans can also carry strains of gut bacteria known to drive production of Th17 cells, and the researchers plan to investigate whether the presence of these bacteria is associated with autism.
Sarah Gaffen, a professor of rheumatology and clinical immunology at the University of Pittsburgh, says the study clearly demonstrates the link between IL-17 and the neurological effects seen in the mice offspring. “It’s rare for things to fit into such a clear model, where you can identify a single molecule that does what you predicted,” says Gaffen, who was not involved in the study.
The research was funded by the Simons Foundation Autism Research Initiative, the Simons Center for the Social Brain at MIT, the Howard Hughes Medical Institute, Robert Buxton, the National Research Foundation of Korea, the Searle Scholars Program, a Pew Scholarship for Biomedical Sciences, the Kenneth Rainin Foundation, the National Institutes of Health, and the Hock E. Tan and K. Lisa Yang Center for Autism Research.
Autism was extremely rare fifty years ago and now it is common. What has changed?
Your elitist attitude has no place on a scientific discipline.
You echo the histrionics of the liberals I engage.
Are you off your meds?
What does WTC7 and structural failure have to do with your COI?
My wife has a bun in the oven and it is gonna get Caesareaned in a month.
I am already wracked with worry. We’ve had several scares and several miscarriages, which really suck.
I should not be reading this type of content.
Content like this is why I stop and buy beer on the way home, and sometimes even those little fire whisky airplane bottles.
One of the great peculiarities of pregnancy can be called the “secondary immune system”. That is, a woman’s normal immune system is too efficient to permit pregnancy, so it is naturally suppressed by her body, and a temporary replacement system, one that will neither see the fetus as an infection or a cancer, takes over.
It is yet to be very well understood, but what is known is that the changeover to the secondary system and back can actually resolve some chronic health problems, yet may cause some new ones.
Do you also believe in AGW? After all 97% of ‘scientist’ agree it’s all our fault. I have an advanced degree in Biology and I was always taught that in science you never say always and you never say never. Obviously they don’t follow that dictum at fancy colleges in Massachusetts. I would say that if what this study says proves to be true then the idea of putting antigens in large doses into small children with still developing, fragile immune systems might be something requiring more research. I am not an anti vaccine person, but when I read the levels of vaccines that babies were exposes to today I was shocked.
Somehow I, both my siblings and most of my friends made it safely into our 60-70’s without ever being exposed to massive levels of vaccinations. Did we suffer through the mumps, chicken pox and measles when we were young, yes, but we all survived, as did our classmates, and developed natural immunity to boot. Could it be that this push for ever increasing levels of vaccination is just a way for big Pharma to develop an nice, steady income stream? Not accusing just asking?
Autism was extremely rare fifty years ago and now it is common. What has changed?
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You name it. So many differences in child-rearing philosophies and actions that it’s difficult to call it child-rearing anymore.
Radical changes in diet also have happened with all of the parent permissiveness.
Not only that, but the tendency to over-diagnose certain conditions creates a syndrome-du-jour.
So before we start blaming things on vaccines and other biochemical hodgepodges, we should look at more prevalent and more severe changes in the neo-Marxist attempts to destroy the family.
Stop worrying. You have a child on the way. They need a brave strong dad
Instead of drinking take a walk with your wife. Enjoy the peace and quiet. It will change
Fifteen minutes to Wapner.
If you cannot elaborate on your gibberish, I must conclude that you are either mentally -challenged or a vaccine sycophant.
So you need to be told when you are being ignored?
And you came back to it in order to show it to everyone
Attention-whore calling the kettle black...
What is your problem?
“What is your problem?”
Now you want sympathy? Clearly you had nothing to contribute prior; go away now.
You are the one who had nothing to contribute
You have tried to pick fights with several posters. You did not address the research sites in the article. You have spent many posts calling people all sorts of names. Hence my question.
Don’t bother replying I am done with you
No, I have spent posts deflecting liberal-like attacks and the only name called was in your direction in response to your own bombastic rhetoric. Reading comprehension is a problem among affected libs; you seem conflicted...seek help.
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