Understanding Brain Adaptation Processes During Alcohol Withdrawal

Alcohol abuse affects at least 14 million Americans, and nearly 35,000 die each year due to chronic alcohol dependence and alcohol withdrawal. At the clinical level, individuals with chronic alcohol dependence experience a variety of physical and emotional consequences upon cessation of alcohol intake that may include severe anxiety, hallucinations, elevated blood pressure, increased heart rate, seizure, tremens, cardiac arrhythmias, or in some cases, sudden death. This collection of symptoms during alcohol withdrawal suggests a role for two interconnected brain regions known to regulate homeostasis and emotion: the nucleus tractus solitarius (NTS) and the central nucleus of the amygdala (CeA), according to mechanisms that are currently not well understood. As a first step towards understanding these mechanisms in the brain, the goal of this work is to identify and characterize the molecular processes of adaptation and regulation in alcohol withdrawal using a combination of experimental and computational techniques. Specifically, we have: (1) utilized emerging high-fidelity, high-throughput techniques to collect dynamic gene expression profiles in the NTS and CeA; (2) developed novel techniques to analyze these data sets, and finally, (3) determined the primary control mechanism for compensation following alcohol blockage of a key brain receptor using a computational model. The results provide a unique systems level understanding of dynamic adaptation processes in the brain during alcohol withdrawal, which may lead to strategies for prevention of the lethal consequences of withdrawal and thereby enable the successful recovery of alcohol dependent individuals.

Advisors: Babatunde A. Ogunnaike¹ and James S. Schwaber² (¹Department of Chemical Engineering, University of Delaware, Newark, DE; ²Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA)