Epigenetic Mechanisms of Memory Dysfunction in AD
In the first portion of the project, Dr. Bero’s team will use cutting-edge genome sequencing techniques to comprehensively define the changes in gene expression that underlie memory formation in the healthy brain. In parallel, the team will measure the levels of an epigenetic marker that is expressed in the brain and is associated with gene expression. In the nervous system, an epigenetic change refers to a structural change in chromosomes that serves to signal and perpetuate altered activity states. These experiments will begin to clarify the mechanisms by which memories remodel neural circuits and will serve as the foundation for the experiments described below.
The second portion of the project seeks to examine the mechanisms by which AD impairs memory formation. To this end, Dr. Bero’s team will use a mouse model that is genetically engineered to develop AD-like changes in the brain and memory dysfunction. Using this mouse model, the team will define the comprehensive changes in gene expression that are associated with AD-related memory impairment and examine whether these changes are accompanied by epigenetic dysregulation.
In the final portion of the project, Dr. Bero’s team will use a new technology termed “optogenetics” to determine whether restoration of neural circuit function during memory formation can restore memory function in a mouse model of AD. Finally, they will examine the mechanisms that underlie this rescue in memory function by determining whether improved memory function is accompanied by a restoration of gene expression and epigenetic profiles.
The expertise of Dr. Bero’s laboratory at MIT resides at the nexus of biological discovery and technological innovation, and his team is thus uniquely positioned to address questions about AD that are otherwise inaccessible. When this project is complete, the team will have generated the first circuit-level analyses of gene expression that underlie memory formation in a healthy brain and in brains affected by AD-like pathology. In addition, they will have determined whether restoration of neural circuit function during memory formation can restore memory function in a model of AD. Together, these data will provide novel insights into the origins of AD and potentially reveal novel strategies for AD treatment.
About the Researcher
Dr. Bero is a Postdoctoral Associate in the laboratory of Dr. Li-Huei Tsai at the Massachusetts Institute of Technology. He completed his Ph.D. at Washington University in St. Louis working with Dr. David Holtzman where he investigated the mechanisms by which specific neural networks are targeted by amyloid-β deposition in Alzheimer’s disease. His current work utilizes a molecules-to-circuits approach to elucidate mechanisms that mediate memory function and dysfunction in normal and diseased brain. In addition to his BrightFocus award, Dr. Bero is the recipient of the Olin Medical Scientist Fellowship and the Hope Center Award for Research in Translational Neuroscience at Washington University in St. Louis.
First published on: Sunday, June 30, 2013
Last modified on: Thursday, June 20, 2013