Gregory Sartor, assistant professor in the Department of Pharmaceutical Sciences, recently received a three year grant from the National Institute on Drug Abuse (NIDA). The grant, titled Neuronal subtype and circuit-specific epigenetic mechanisms in addiction, involves studies that will utilize novel, molecular and genetic tools to dissect epigenetic factors that regulate drug-seeking behaviors in animal models of addiction.
“For years, a hallmark of pre-clinical addiction research has been to non-specifically manipulate cells within the brain or a brain region,” says Sartor. “However, it has become evident that brain regions associated with reward/addiction, such as the nucleus accumbens, are composed of diverse cell types that have differential molecular compositions, connections, and involvement in drug-seeking behaviors. Thus, non-specific observation or manipulation of such regions is not sufficient to fully understand the complex nature of the substance abuse.”
By identifying precise mechanisms that underlie addiction, Sartor hopes that this reseach will lead to the development of new effective treatments.
In addition, Sartor’s research titled, Enhancement of BDNF expression and memory by HDAC inhibition requires BET bromodomain reader proteins, was recently published in the Journal of Neuroscience. Sartor says that brain-derived neurotrophic factor (BDNF) is a key mediator of multiple aspects of brain function including neurodevelopment, synaptic structure, neurotransmitter release, and learning and memory. Despite the long-established relationship between altered levels of BDNF and multiple neurological and psychiatric disorders, mechanisms that regulate the expression of BDNF are not completely understood. In the current study, Sartor and colleagues identified a novel interplay between an epigenetic reader protein (called BRD4) and an eraser protein (called HDAC3) that is necessary for increased expression of BDNF and improved memory. “By identifying novel regulators of BDNF expression, these results will enhance our understanding of how epigenetic mechanisms contribute to brain health and disease,” he says.