Prader-Willi (PWS) and Schaaf-Yang syndromes (SYS) are disorders that are both caused by alterations of the MAGEL2 gene, which is either completely missing (PWS) or non-functional (SYS). Working with PWS and SYS mouse models, Dr. Schaaf will investigate the function of a brain ‘support cell’ (astrocytes), which have recently been found to be activated by oxytocin. They will analyze the 3D structure and function of these astrocytes and will investigate how they modulate neuronal activity in different brain regions, in the typical situation and when MAGEL2 is deficient. This approach could yield important information about how changes in astrocyte function in PWS and SYS may lead to cognitive and/or social manifestations in both disorders.
Dr. Theresa Strong, Director of Research Programs, shares details on this project in this short video clip.
Watch the full webinar describing all 9 research projects funded in this grant cycle here.
Prader-Willi (PWS) and Schaaf-Yang syndromes (SYS) are diseases that are both caused by alterations affecting the gene MAGEL2, which is either completely missing or non-functional. Individuals suffering from PWS or SYS display unique behavioral traits, including learning disabilities and altered social behavior.
To be able to better study these two diseases, genetically modified mouse models have been created that manifest behavioral patterns replicating the social deficits of PWS and SYS. Working with these mouse models, researchers found that the lack or dysfunction of the Magel2 gene results in changes to neurons producing the oxytocin hormone. Intriguingly, oxytocin administration appears to ameliorate several of the symptoms associated with PWS and SYS. This proposal aims to investigate the effect of oxytocin on star-shaped cells within the brain called astrocytes, which have recently been found to be activated by oxytocin.
We will analyze the three-dimensional structure and function of these astrocytes to better understand their role in PWS and SYS and will investigate how these astrocytes modulate neuronal activity in different brain regions. This approach is entirely novel and could yield important information about how a previously ignored cell type in the brain plays a critical role in brain dysfunction, leading to cognitive and/or social manifestations in these two diseases.
Christian Schaaf, MD, Ph.D
University Hospital Heidelberg
Christian Schaaf, MD, Ph.D.