Autism-like behavior reversed in laboratory mice
MIT scientists havesuccessfully reversed autistic-like behavioral patterns in mice. Thestudy focused on a gene called Shank3, which is missing in 1 percentof individuals suffering from autism, and is believed to be vital for the development of a healthy adult brain.
Autism is a term for agroup of disorders that arise from a diverse range of genetic causesthat work to prevent the brain from developing normally, often makingthe simplest of social interactions incredibly difficult.According to the US Centers for Disease Control and Prevention(CDC), instances of autism have risen 10-fold over the space of 40years, with roughly 1 in 68 American children currently thought to be on theautistic spectrum.
The new MIT researchmay lead to gene therapy treatment for some patients that couldalleviate certain behavioral defects synonymous with autism. Priorto the study, the Shank3 protein was known to be located in thebrain's synapses, where it acts as a scaffold for other proteins,organizing them and allowing them to work together to allow a neuronto form a cohesive response to an incoming signal.
Scientists haveobserved that mutations or deficiencies of Shank3 in the brain cancause synaptic disruptions in mice, leading to some of the irregularbehavioral patterns linked to autism. Furthermore, researchers havenoted a lower quantity of dendritic spines in micesuffering from a Shank3 deficiency, with the abnormality becomingmore pronounced in the striatum.
For the purposes of therecent study, scientists genetically engineered mice with inactiveShank3 genes. As the mice developed, they exhibited a number ofautism-like behaviors including an aversion to social situations,compulsive and repetitive behavior, and anxiety.
Between two to fourmonths after birth, the team introduced a breast cancer drug known astamoxifen into the food of the mice, which had the effect ofreactivating the Shank3 in the rodents' synapses.
Soon after, the teamnoticed alterations in the behavior of the mice, including anabsence of repetitive actions and an increase in socializing. Micethat were introduced to the tamoxifen at an earlier stage alsoappeared to display a reduction in anxiety and improved motor skills.
The results of thestudy display a surprising level of elasticity on a cellularlevel, with the brain proving to be capable of rewiring itself andgenerating new dendritic spines.
The next step for theteam will be to discern at what point circuits in the brain relatingto anxiety and motor function become too damaged to respond to thenewly activated Shank3 proteins.
"Some circuits aremore plastic than others," states lead author of a paper on thefindings Guoping Feng, a professor of brain and cognitive sciences atMIT. "Once we understand which circuits control each behavior andunderstand what exactly changed at the structural level, we can studywhat leads to these permanent defects, and how we can prevent themfrom happening."