(342) Molecular Transcriptomic Effects of General Anesthesia on Gene Expression in Frontal Lobe, Hippocampus, and Amygdala after Administration of Ketamine and Isoflurane

Abstract

General anesthesia and monitored sedation are vital to nearly all procedural aspects of modern medicine. Inhaled agents such as halogenated gases have long been an integral aspect of anesthesia. In recent years, the noncompetitive NMDA antagonist and dissociative anesthetic ketamine has seen increasing utilization in general anesthesia, as well as in the treatment of chronic pain and depression. The use of ketamine for such chronic conditions has raised questions into its addictive potential, and its potential role in the treatment of existing addictions. New investigations using high density electrical recordings and other multidimensional techniques have led to a clearer understanding of how these agents work, and how they can be utilized to fill clinical needs. To further study their effects at the molecular level, we used deep RNA sequencing to examine the time course (1hr, 10hr, or 10hr + 24hr recovery) of gene changes induced in the frontal cortex, hippocampus, and amygdala during ketamine or isoflurane administration. When compared to isoflurane, the transcriptional signature of ketamine showed similarities and differences that suggested region-specific gene regulation patterns that highlight the molecular underpinnings of the broad clinical uses of ketamine. The evaluation of brain regions subserving the diverse functions of learning and memory, executive function, and emotional-affective dimensions yielded insight into the neural localization of anesthetic actions and potential vulnerabilities associated with general anesthesia. Our investigation demonstrates unique region-specific and time-dependent transcriptional signatures that bridge molecular and systems level findings to expand current understanding of the shifts in neuronal activity associated with general anesthetics and their downstream effects.