Autism Research: November 28, 2014 Week in Review

ResearchIs a missing gene the link to autism?Researchers at the University of Leeds had previously discovered that people with autism are lacking in the gene neurexin-II and had studied mice with the same condition that showed a lack of social skills. Now Dr Steven Clapcote, who published the study in  Translational Psychiatry told: “In other respects, these mice were functioning normally. The gene deficiency mapped closely with certain autism symptoms.” The researchers now have an animal model in which they can investiagte and research for new autism treatments. Primarily they looked at how neurexin-II affected the brain. The mice who were affected  had much lower levels of the protein Munc18-1 situated in the brain whose job is to help release neurotransmitter chemicals across synaptic connections, so in theese mice this process could be affected  and possibly be the cause autism in some cases. Dr Clapcote added: “Not all people with autism will have the neurexin-II defect, just as not all will have the neuroligin defect, but we are starting to build up a picture of the important role of genes involved in these synapse communications in better understanding autism.”James Dachtler et al. ‘Deletion of α-neurexin II results in autism-related behaviors in mice is published in Translational Biology’ is published in Translational Psychiatry. DOI: 10.1038/TP.2014.123

Can a new fragile x study offer insights into autism treatment?

A drug that is being tested for the treatment of cancer may be able to help individuals with the inherited form of autism, fragile x. Researchers believe that the drug may be able to reverse behavioral symptoms.  The naturally occurring chemical, cercosporamide is able to  block the pathway which can improve the social skills in mice who have the condition. The University of Edinburgh team and McGill University in Canada were able to identify a key molecule, eIF4Em that can cause behavioural symptoms including learning difficulties, delays in speech and language and social difficulties. The molecule  eIF4E regulates production of a specific enzyme called MMP-9, that helps to  re-order  connections between synapses. This disruption in communication between the brain cells is what leads to behavioral changes. Cercosporamide at present is being tested as a treatment for  acute myeloid leukemia and findings also believe it could be used for those with fragile x. Professor Nahum Sonenberg said: “We found that eIF4E regulates the production of an enzyme called MMP-9, which breaks down and re-orders the connections between brain cells called synapses. Excess MMP-9 disrupts communication between brain cells, leading to changes in behaviour.”

C. G. Gkogkas et al. Pharmacogenetic Inhibition of eIF4E-Dependent Mmp9 mRNA Translation Reverses Fragile X Syndrome-like Phenotypes. Cell Reports, 27 November 2014.

Study explains why people with autism may see faces differently

Researchers at Hôpital Rivière-des-Prairies and the University of Montreal have recently conducted a study into the way individuals with ASD gather information. Lead author of the study, Baudouin Forgeot d’Arc told, “The evaluation of an individual’s face is a rapid process that influences our future relationship with the individual,” The study wanted to try and understand how people with ASD recognise and use facial features.  71 individuals were involved in the study, 38 individuals were in a control group and 33 in the ASD group, none of the participants had intellectual disabilities. Each individual was shown  36 pairs of photographic images and their social judgment was evaluated by asking  which neutral faces had  appeared to be “kind”. The findings suggested that the reaction of the ASD participants were mixed and not predictable when compared to the control group. What the findings suggest is that the way individuals with ASD gather information about a person’s face is critical. Forgeot d’Arc told of the findings, “We now want to understand how the gathering of cues underpinning these judgments is different between people with or without ASD depending on whether they are viewing synthetic or photographic images. Ultimately, a better understanding of how people with ASD perceive and evaluate the social environment will allow us to better interact with them.”

The role of serotonin in assembling brain circuits

Past research has found that having a poor serotonin regulatory system can increase the risks of gaining autism and depression as well as anxiety disorders. Genetic variations found in the serotonin system can indeed interact with the stress experienced during foetal stages of development and early childhood, which can increase risks of developing psychiatric problems later on. Alexandre Dayer and his team at UNIGE’s Faculty of medicine looked at a receptor for this particular neurotransmitter in relation to forming brain circuits. What they found was that  this receptor, “was indispensable in order for neurons to find their correct location in the developing cortex.”   Larger studies will be needed on the role that serotonin plays in brain development. Alexandre Dayer told that the study raises some very important questions,  “including about the use of medicine by pregnant women which could modify foetal serotonin levels. We also want to understand how early stress acts on this receptor and modifies the function of the neurons in question.”

Scientists find that abnormal neural connections causes motor coordination issues in autism

Scientists at the University of Chicago have found that abnormal neural connections may likely cause motor coordination difficulties  in individuals with ASD. What was found was a malfunctioning neural circuit that they reported in  Nature Communications Nov. 24. Senior author of the study, Christian Hansel, PhD, told:”We have identified synaptic abnormalities that may play a role in motor problems typically seen in children with autism.”  80 per cent of children with ASD  have some kind of motor coordination issue, this may be clumsiness or difficulties involving the control and movement of the eye.  For the study researchers used a mouse model for one of the most common  genetic abnormalities, the human 15q11-13 chromosomal duplication and focused upon the cerebellum,the area of the brain responsible for motor control. Difficulties were found in unstable gait and in the impairment of  motor learning.

 Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism,” Nature Communications, 2014.