Auditing autism

The study focused on the neuroligin-3gene. Neuroligins are proteins responsible for mediating theformation of synapses between neurons and specifying the functions ofthose synapses. Alterations or mutations in the genes that encodeneuroligins are associated with autism as well as other cognitivedisorders, and neuroligin-3 is one of the over 300 candidate genes inwhich mutations are implicated with a risk for developing autism.

"Neuroligin-3 is involved in theformation of synapses, the contact junctions between nerve cells. Instudies using neuroligin-3 knockout mice we have now identified adefect in synaptic signal transmission that interferes with thefunction and plasticity of neuronal circuits," Peter Scheiffele,professor at the University of Basel Biozentrum and lead investigatorof the study, said in a press release. "These negative effects areassociated with increased production of a specific glutamatereceptor, mGlu1, which modulates signal transmission between neurons.An excess of these receptors inhibits the adaptation of synapticsignal transmission during the learning process, thus disrupting thedevelopment and function of the brain in the long term."

After the researchers reactivatedneuroligin-3 in the mouse models, the nerve cells were shown todecrease the production of mGlu1 to regular levels, and as a result,the structural defects that present in autistic brains disappeared.

The findings have applicability inconditions other than autism, as the paper's abstract notes thatmany monogenic syndromes such as fragile X syndrome, of which autismis a symptom, "have revealed specific defects in synapticplasticity."

"These findings represent asignificant step in enabling the identification of medicines forautism and highlight the pivotal role of public–privatepartnerships in advancing our understanding of this complex disease."Luca Santarelli, head of Neuroscience Research at Roche, said in apress release. "These results are of major importance because theysupport the notion that, although many genes are involved in autism,there is a convergence at the level of the synapse which can betargeted for therapeutics."

Moving forward, in EU-AIMS, a projectsupported by the European Union, research groups from the Biozentrumand Roche are collaborating with industry partners to examine thepotential of glutamate receptor antagonists as a treatment forautism.

There is currently no cure for autism,and treatment for the disorder is limited to alleviating the symptomsby way of behavioral therapy and other treatments.

Autism is a neurological developmentaldisorder that presents in early childhood. Autism and autism spectrumdisorder are characterized by difficulties with social interaction,verbal/nonverbal communication and repetitive behaviors. Intellectualdisability, difficulties in motor coordination and attention andphysical health issues are also common, according to the AutismSpeaks website. The U.S. Centers for Disease Control and Prevention(CDC) state that one in 88 American children fall somewhere in theautism spectrum, with roughly one in 54 boys and one in 252 girlsdiagnosed with the condition. More than two million people areaffected by autism spectrum disorders (ASDs) in the United States alone, with tens of millionsaffected worldwide, notes Autism Speaks. The economic burden isconsiderable, with the CDC noting that "intensive behavioralinterventions for children with ASDs cost $40,000 to $60,000 perchild per year."

In addition to Scheiffele, the paper'sauthors include Stephane J. Baudouin, Julien Gaudias, Stefan Gerharz,Laetitia Hatstatt, Pradeep Punnakkal and Kaspar Vogt of theBiozentrum of the University of Basel; Kuikui Zhou and Chris I. DeZeeuw of the Department of Neuroscience, Erasmus MC; and Kenji F.Tanaka and Rene Hen of the Department of Neuroscience at ColumbiaUniversity.