How Immune Response in Pregnancy May Lead to Brain Dysfunction in Offspring

ScienceDaily (Oct. 12, 2010) A pregnant woman's immune response to viral infections may induce subtle neurological changes in the unborn child that can lead to an increased risk for neurodevelopmental disorders including schizophrenia and autism. Research published in the online journal mBio provides new insights into how this may happen and suggests potential strategies for reducing this risk.

"Infection during pregnancy is associated with increased risk of damage to the developing nervous system. Given that many agents have been implicated, we decided to focus on mechanisms by which the maternal immune response, rather than direct infection of the fetus, might contribute to behavioral disturbances in the offspring of mothers who suffer infection during pregnancy," says W. Ian Lipkin of Columbia University, senior author on the study.
To better understand how the immune response causes these neurological changes, the researchers exposed pregnant mice to a synthetic molecular mimic of a replicating virus. Offspring of the exposed mice had impaired locomotor activity compared to controls. Further testing determined that the exposure inhibited embryonic neuronal stem cell replication, affecting brain development.
They also looked at the potential role of an immune protein known as Toll-like receptor 3 (TLR3) which is commonly activated in viral infections. Using TLR3-deficient mice they determined that the effects of exposure were dependent on TLR3. They also investigated whether the drug carprofen, a non-steroidal anti-inflammatory drug, would have any effect. Pretreatment with the drug abrogated the effects of exposure.
"Our findings provide insights into mechanisms by which maternal infection may induce subtle changes in brain and behavior and suggest strategies for reducing the risk of neuropsychiatric diseases following exposures to infectious agents and other triggers of innate immunity during gestation," says Lipkin.
Editor's Note: This article is not intended to provide medical advice, diagnosis or treatment.

My dad had Hep A when I was in utero so they gave my mother gammaglobulin back int he 60's before they screened blood well.

She has terrible GFS and I was born preemie and had full blown disabling CFS by age 14.

It's been a slow ride to hell.
Immune Protein Linked to Abnormal Brain Development; May Provide Clues
to Schizophrenia and Autism
ScienceDaily (Oct. 14, 2010) UCLA scientists have discovered that
exposing fetal neurons to higher than normal levels of a common immune
protein leads to abnormal brain development in mice.
Published Oct. 14 in the online Journal of Neuroimmunology, the finding
may provide new insights into factors contributing to human neurological
disorders like schizophrenia and autism.
The researchers studied a protein called major histocompatibility
complex, or MHC. The protein plays a dual role in the body: It helps the
immune system to identify infected cells, and it enables neurons to make
the right connections with each other in the brain.

"When neurons sense infection or damage to the brain, they produce more
MHC," said Daniel Kaufman, professor of molecular and medical
pharmacology at the David Geffen School of Medicine at UCLA. "We wanted
to explore whether higher levels of MHC affect how the brain develops."

Kaufman and his colleagues studied the development of mice whose neurons
were genetically engineered to produce more MHC than normal.
Focusing on two key regions of the brain, the researchers looked at
neurons that process vision and neurons involved in learning and memory.
Next, the team compared these cells with their counterparts in normal
What the scientists saw confirmed their hunch.
"The mice whose neurons produced extra MHC showed subtle changes in the
connections between those neurons and other neurons in both brain
regions," Kaufman said.
The UCLA finding could be of relevance in unraveling the origins of
schizophrenia and autism, he noted.
"Infections in pregnant women have been associated with slightly higher
risks for schizophrenia and autism in their children," he said. "Subtle
changes in brain development due to excess MHC may explain this
Kaufman noted that female mice that contract infections during pregnancy
also often give birth to offspring with behavioral abnormalities similar
to autism and schizophrenia.
"We suspect that infection stimulates the mother's immune system to
produce molecules that act like distress signals -- they circulate
through her blood and then enter the developing brain of the fetus," he
said. "There, they alert neurons to make more MHC, which our study shows
can lead to altered neuronal circuitry."

"This finding gives us greater insight into the role that MHC plays in
the nervous system and may enhance our understanding of the factors that
can contribute to neuropsychiatric disorders like autism and
schizophrenia," Kaufman said.
The study was supported by funding from the National Institute of
Neurological Disorders and Stroke. Kaufman's co-authors included
Zhongqi-Phyllis Wu, Lorraine Washburn, Tina Bilousova, Maia
Boudzinskaia, Nathalie Escande-Beillard, Jyes Querubin, Hoa Dang,
Cui-Wei Xie and Jide Tian, all of UCLA.
Editor's Note: This article is not intended to provide medical advice,
diagnosis or treatment.