Signs of autism generally begin to appear around 18 months of age and can include ritualistic movements, impaired social skills, repetitive actions, along with a number of other symptoms that that initially may go undetected. It is believed autism is the result of mis-wiring in connections of the brain as it develops.
Rewire the Autism Brain
Many experts believe the potential rewire the autism brain exists if the autism is diagnosed early enough before the faulty circuits become permanently fixed. However, a recent study indicates that even after that window closes, there is the potential to repair at least one malfunctioning circuit. This is exciting news for parents – the idea that there is some hope to repair the abnormal brain circuits is welcome news.
The results from this research could change the way professionals are looking to treat children who are diagnosed with autism, and there is no question that these changes may be beneficial to autistic children.
According to developmental neurobiologist Peter Scheiffele of the University of Basel in Switzerland, autism doesn’t result from a handful of “culprit” genes that point to a treatable flaw. Instead, patients appear to carry mutations in one out of dozens, even hundreds of risk genes. “This genetic complexity is a huge issue with respect to developing treatments [for autism],” Scheiffele says. To complicate the picture further, autism is not always an isolated disorder; it’s often a common feature in syndromes that otherwise differ drastically. For example, in fragile X syndrome, a form of mental retardation, about 25% of patients are also autistic.
Scheiffele and his colleagues were studying the neuroligin-3 (Nlgn3) gene, which is involved in building the synapses, between neurons. Many researchers believe that autism begins at the synapse, and mutations in Nlgn3 have appeared in some forms of the disorder. Sheiffele’s team focused on synapses in the cerebellum, which is a part of the brain that controls movement. However, according to recent research, it may also be involved in social behavior. Abnormalities in this region could play a role in both the unusual movements and the social problems that are seen in autistic children.
To get a better handle on the role of Nlgn3, the scientists studied mice whose Nlgn3 genes were engineered with an on-off switch, called a promoter region, and controlled by the antibiotic doxycycline. The animals were raised with the drug in their drinking water, which kept the switch in the off position. With the Nlgn3 gene disabled in the mice, the neurons in their cerebellum made the abnormal connections seen in the autistic brain.
The researchers’ were surprised to discover the lack of Nlgn3 led to the over activation of a receptor abbreviated as mGluR1α. This receptor is an element of a pathway that is also disrupted in fragile X syndrome, though the mutations are the result of a completely different gene. In the mice, the overabundance of these receptors caused the neurons to make synaptic connections that were in the incorrect places.
Researchers then withdrew the doxycyline to determine if turning the Nlgn3 gene back on corrected these problems, and it worked: With Nlgn3 functioning, the levels of the extraneous receptor once again receded back to normal, and the misplaced synapses started to vanish.
“Our finding demonstrates that there is still flexibility after the ‘critical window’ of brain development,” Scheiffele says. “It raises the question: To what extent can a mis-wired brain be corrected?”
Correcting abnormalities in Motor Skills
Next the team plans to determine whether they can correct abnormalities in motor skills with a treatment that resembles that used on the engineered mice. The team is currently studying whether drugs that block the mGluR1α receptor will have the same outcome as when the Nlgn3 gene is genetically controlled, which is not a human treatment option.
“This study holds out hope for children and even adults with developmental disorders. Maybe their conditions aren’t set in stone and can be treated,” says neuroscientist Kimberly Huber of the University of Texas Southwestern Medical Center in Dallas. Huber adds that drugs that block a similar receptor, mGluR5, are in clinical trials to treat fragile X syndrome.
1)Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism
2) Negative Allosteric Modulation of the mGluR5 Receptor Reduces Repetitive Behaviors and Rescues Social Deficits in Mouse Models of Autism