The likelihood of drugs being developed to treat autism has moved closer. It follows the discovery of a gene defect that causes changes in the brain that lead to atypical social behaviour similar to that found in autism.
Cecilia Giulivi (pictured), professor of molecular biosciences in the UC Davis School of Veterinary Medicine in California, who led the research, said: “A number of genes and environmental factors have been shown to be involved in autism, but this study points to a mechanism – how one gene defect may trigger this type of neurological behaviour.
“Once you understand the mechanism, that opens the way for developing drugs to treat the condition.”
The research reveals how advances in neuroscience, molecular biology, genetics, pharmacology and behavioural sciences are helping us to understand brain function.
Scientists were already aware that the gene is defective in children with autism, but until now were unaware of its effect on neurons in the brain.
The defective gene appears to disrupt neurons’ use of energy, the critical process that relies on the cell’s mitochondria, their molecular energy factories.
Giulivi has long been researching the link between mitochondria dysfunction and autism (see Autism Eye, Spring 2011issue). In this latest study Giulivi and fellow scientists tweaked a gene called pten in mice so that neurons lacked the normal amount of pten’s protein. The scientists detected malfunctioning mitochondria in the mice just four to six weeks after birth.
By 20-29 months, DNA damage in the mitochondria and disruption of their function had increased dramatically. The mice began to avoid contact with each other and engaged in repetitive grooming behaviour. Mice whose gene remained unchanged displayed no such behaviour or mitochondria malfunctions.
The antisocial behaviour was most pronounced in the mice at an age comparable in humans to the early teenage years, when schizophrenia and other behavioural disorders become most apparent, Giulivi said.
The research also showed that when defective, pten’s protein interacts with the protein of a second gene known as p53 to dampen energy production in neurons. This severe stress leads to a spike in harmful mitochondrial DNA changes and abnormal levels of energy production in the cerebellum and hippocampus, brain regions critical for social behaviour and cognition.
Pten mutations have previously been linked to Alzheimer’s disease, as well as a spectrum of autism disorders. This new research reveals that when the pten protein was insufficient, its interaction with p53 triggered deficiencies and defects in other proteins that have also been found in people with learning disabilities, including those affected by autism.
The study was supported by the US-based Autism Speaks Foundation, the Mind Institute, the Elsa U Pardee Foundation and the National Institute of Environmental Health Sciences.
Published: 11 August 2012
