Genetic clues to altered brain “wiring” in autism identified
Autism is a highly complex puzzle, a tangle of both genetic and environmental factors. In recent years scientists have begun to explore how mutations in a pathway that regulates growth in the developing brain are linked to the condition.
In animal models, scientists from Florida branch of The Scripps Research Institute identified that a mutation in PTEN, one of the genes that controls the mTOR developmental pathway, can cause a particular form of autism called macrocephaly/autism syndrome.
“When PTEN is mutated, we find that neurons that project from the prefrontal cortex to the amygdala are overgrown and make more synapses,” said TSRI Associate Professor Damon Page. “In this case, more synapses are not necessary a good thing because this contributes to abnormal activity in the amygdala and deficits in social behavior.”
Page and his team used animal models of the syndrome to study how mutations in PTEN affect the development and function of the brain. Their study also showed that targeting the activity of the mTOR pathway shortly after birth, a time when neurons are forming connections between these brain areas, can block the emergence of abnormal amygdala activity and social behavioral deficits. Likewise, reducing activity neurons that project between these areas in adulthood can also reverse these symptoms.
“Given that the functional connectivity between the prefrontal cortex and amygdala is largely conserved between mice and humans,” said TSRI Graduate Student Wen-Chin Huang, the first author of the study, “we anticipate the therapeutic strategies suggested here may be relevant for individuals on the autism spectrum.”
Extrapolation results from animal models to humans, especially in the case of highly complex conditions like autism. However, these findings have implications for individualised approaches to treating or managing autism. “Even within individuals exposed to the same risk factor, different strategies may be appropriate to treat the symptoms of autism in early development versus maturity,” explained Page.