Researchers Reveal Gene UBE3A and Neural Circuits Contribute to Impaired Sociability in Selected Autism Spectrum Disorder
Scientists at the Beth Israel Deaconess Medical Center (BIDMC) published a study that shows that the gene UBEeA and neural circuits are contributing factors to impaired sociability in some forms of Autism Spectrum Disorder. The study is geared towards finding effective interventions for patients with the condition.
In the study published in the journal Nature, Dr. Matthew P. Anderson, director of Neuropathology at BIDMC, led a group of researchers to determine how a gene that has been linked to a common form of autism operates in certain cells in the brain to impair sociability. The group selected the gene UBE3A for their research.
A number of copies of the gene UBE3A clinically dubbed isodicentric chromosome 15q can cause a form of Autism Spectrum Disorder in humans. However, the lack of the gene UBE3A causes a developmental disorder called Angelman's syndrome.
Science Daily reports that the Anderson and his team utilized engineered mice having extra copies of the gene UBE3A. According to Anderson, the team found out that the increase in the number of UBE3A gene copies interacted with about 600 other genes.
The increase in the number of UBE3A gene copies resulted in the engineered mice having impaired sociability. The test subjects also have "heightened repetitive self-grooming, and reduced vocalizations with other mice," a telltale sign of some forms of Autism Spectrum Disorder in humans.
Further analysis of the protein interactions between the gene UBE3A and the genes altered in some forms of Autism Spectrum Disorder in humans, suggests that the increase in doses of UBE3A represses the Cerebellin genes. The Cerebellin genes interact with other autism genes to facilitate glutamatergic synapses, the sections in which the neurons communicate with each other via the neurotransmitter glutamate.
The team of researchers selected Cerebellin 1 (CBLN1) as the potential mediator of the UBE3A genes' effect. Anderson said they were able to reconstitute the social deficits after they deleted the CBLN1 in glutamate neurons, therefore proving that CBLN1 was the gene being repressed by the UBE3A.
This breakthrough was backed by another series of experiments to strengthen the link between EBE3A and CBLN1 and their relation to seizures and impaired sociability. The team at BIDMC concluded that by deleting the UBE3A gene, upstream from Cerebellin genes, the seizure-induced social impairments are prevented. Also, it can block the seizures ability to repress CBLN1.
According to Anderson what they discovered is, in some way, a toggle switch for sociability. It means that inhibiting the neurons results in abolishing sociability. Conversely, by turning on the neurons, the result of the study show that sociability can be prolonged and magnified. Also, it can rescue seizure and UBE3A gene-induced social impairments.
The result of this study is promising, something that Anderson hopes would be translated into a treatment that could ultimately help cure or suppress impaired sociability in selected Autism Spectrum Disorder.