Category: Autism

 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.

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Journal Reference:

1. J. De Miranda, K. Yaddanapudi, M. Hornig, G. Villar, R. Serge, W. I. Lipkin. Induction of Toll-Like Receptor 3-Mediated Immunity during Gestation Inhibits Cortical Neurogenesis and Causes Behavioral Disturbances. mBio, 2010; 1 (4): e00176-10 DOI: 10.1128/mBio.00176-10.

Children with autism will tell white lies to protect other people's feelings and they are not very good at covering up their lies, according to a Queen's University study.

The study, conducted by psychology professor Beth Kelley and developmental psychology PhD student Annie Li, is one of the first scientific studies of lying and autism.

"The results are surprising because there is a notion that children with autism have difficulty appreciating the thoughts and feelings of other people, so we didn't expect them to lie to avoid saying things that may hurt others," says Dr. Kelley.

In one test, children with autism were told they were going to get a great gift, and were then handed a bar of soap. When asked if they liked their gift, most nodded or said yes instead of saying they were disappointed to get soap.

Researchers refer to this as pro-social lies told to maintain good relations with others.

In a second test, children were given audio clues and asked to guess a hidden object. Most guessed the easy clues, a chicken when they heard a chicken clucking — but an intentionally difficult clue (Christmas music and an Elmo doll) — was used as a test for lying.

After the Christmas music was played, the tester left the room. The tester returned and asked the children if they had peeked at the object. Both autistic and non- autistic children were equally likely to lie that they had not peeked. But when asked what they thought the object was, children without autism realized giving the correct answer would reveal they peeked so they were more likely to lie and say "Santa" or "Christmas tree."

The study has been accepted for publication to Journal of Autism and Developmental Disorders.

Angela D. Evans and Kang Lee from the University of Toronto also took part in the study.

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Journal Reference:

1. Annie S. Li, Elizabeth A. Kelley, Angela D. Evans, Kang Lee. Exploring the Ability to Deceive in Children with Autism Spectrum Disorders. Journal of Autism and Developmental Disorders, 2010; DOI: 10.1007/s10803-010-1045-4

By creating a better way to see molecules at work in living brain cells, researchers affiliated with MIT's Picower Institute for Learning and Memory and the MIT Department of Chemistry are helping elucidate molecular mechanisms of synapse formation. These studies could also help further understanding of how synapses go awry in developmental diseases such as autism and Fragile X syndrome. The study will appear in the Oct. 7 issue of Cell.

Using the new technique, which is more accurate and sensitive than existing methods, the researchers found that certain protein-protein interactions can affect early phases of synapse maturation. Their work will help scientists understand exactly how two adjacent neurons form a synapse — the meeting point where information transfer among brain cells occurs. This method provides information on the dynamics of proteins in synapses on a minute-by-minute time scale, the researchers said.

"How nascent contacts mature into excitatory or inhibitory synapses is an area of intense interest," said Amar Thyagarajan, Autism Speaks Postdoctoral Fellow in the laboratory of Alice Y. Ting, associate professor of chemistry. "Trans-synaptic signaling complexes seem like a good place to start looking for clues to this process since they mediate signaling into the pre- and post-synaptic cells during this process."

Study co-authors Thyagarajan and Ting are Picower Institute affiliates.

The researchers studied the interaction of the proteins neurexin and neuroligin on the surface of neurons. These adhesion molecules–two of many in the brain that regulate synapse formation, maturation, function and plasticity–not only function as the "glue" that hold neurons together but also mediate signaling so that the appropriate molecular components are recruited for the pre- and postsynaptic cells.

Neurexins and neuroligins can be thought of as a chemical bridge and communication network that spans the synaptic cleft.

Called BLINC (Biotin Labeling of Intercellular Contacts), the new technique creates a fluorescent signal only when neurexin and neuroligin interact. "The only way for a BLINC signal to occur is when two neurons contact each other," Thyagarajan said.

For a long time, it had been known that neurexins and neuroligins are important for synapse maturation. However, their exact function was unclear since most previous studies used indirect methods such as manipulating gene expression to infer function.

"Our motivation was that if we could come up with a way to directly observe this complex, then maybe we could better understand its function in synapse maturation," Thyagarajan said.

"We developed BLINC to visualize this complex in live synapses in culture. We then used BLINC in different modalities to discover that synaptic activity causes the neurexin-neuroligin complex to grow in size," he said. "This growth is necessary for the recruitment of AMPA receptors to young synapses.

"AMPA receptor recruitment is a hallmark of excitatory synapse maturation, so our study demonstrated how a trans-synaptic complex can affect early phases of synapse maturation," Thyagarajan said.

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Journal Reference:

1. Amar Thyagarajan and Alice Y. Ting. Imaging Activity-Dependent Regulation of Neurexin-Neuroligin Interactions Using trans-Synaptic Enzymatic Biotinylation. Cell, 7 October, 2010 DOI: 10.1016/j.cell.2010.09.025