Essential UBE3A protein deficient in patients crucial for early brain network development

In a groundbreaking study published in the journal JCI Insight, researchers have shed light on the crucial role of the UBE3A protein in the development of the dorsomedial striatum (DMS) during early postnatal brain development, particularly in relation to Angelman syndrome.

The study, led by Dr. X and Dr. Y from the University of Z, alongside the ABC Neuroscience Institute, focused on the DMS in a mouse model to better understand the disruptions in brain circuitry observed in Angelman syndrome.

Angelman syndrome, a neurological disorder caused by mutations that result in a lack of the UBE3A protein, is characterised by motor learning deficits and abnormalities in brain circuitry. In this study, the researchers aimed to better understand how and when neurological abnormalities appear in Angelman syndrome, with the goal of designing therapies.

The findings highlight an important role of UBE3A during a critical period of brain maturation, specifically around three weeks after birth in mice. If UBE3A is not expressed until about two months after birth in genetically engineered Angelman mouse models, changes in nerve activity persist even with normal levels of UBE3A.

The DMS, a part of the brain involved in the integration and selection of voluntary behavior, specifically coordinating goal-directed actions, and the early phases of motor learning, appears to be particularly vulnerable during this critical period. In Angelman model mice, DMS development appears normal for the first two weeks after birth, but abnormalities are detectable by the third week of life.

Interestingly, mice with normal UBE3A expression during early brain development, who then are treated to stop expressing the protein, show no significant abnormalities on the lever press test, a measure of learning ability. However, in genetically engineered Angelman mouse models, normalizing UBE3A protein expression at 21 days after birth can normalize neuronal activity in the DMS, leading to improvements in the lever press test.

The researchers stressed the need for further work to understand how these mouse results might translate to people and the need for more work to understand the effects of Angelman syndrome in specific areas of the brain. They also highlighted the critical window for therapeutic intervention in Angelman syndrome as not yet well understood.

The study offers promising insights into the development of the dorsomedial striatum region in relation to Angelman syndrome, paving the way for future research and potential therapies.

Essential UBE3A protein deficient in patients crucial for early brain network development