Talk abstracts
Talk on Friday 12:50-01:05pm submitted by Nicholas Deems
Post-surgical morphine prolongs hippocampal dysfunction in aged rats: Implications for neuroinflammation and neuronal structure
Nicholas P. Deems (Neuroscience Graduate Program, Ohio State University), Stephanie M. Muscat (Institute for Behavioral Medicine Research, Ohio State University ), Heather DAngelo, Meagan M. Kitt, Nathan D. Andersen, Shaelyn N. Silverman (University of Colorado Boulder), Peter M. Grace (MD Anderson Cancer Center, University of Texas ), Linda R. Watkins, Steven F. Maier (University of Colorado Boulder ), Ruth M. Barrientos (Department of Psychiatry and Department of Neuroscience, Ohio State University )
Abstract:
Post-operative cognitive dysfunction (POCD) is a constellation of impaired cognitive symptoms that can occur following surgery, most typically in elderly individuals. Cognitive impairment can last days to months with more persistent durations associated with greater susceptibility to mortality and dementia. Mechanisms driving susceptibility for persistent POCD are not well understood. Preclinical models have only recapitulated shorter-durations of post-surgical memory impairments and these models overlook the common use of post-operative opioids. Here we report that treatment with post-surgical morphine robustly impairs hippocampal function for at least eight-weeks in aged rats that underwent an exploratory abdominal surgery (i.e., laparotomy). Short-term memory remained intact, suggesting that these three factors (age, surgery, and morphine) combine to compromise memory processes critical for long-term memory formation. Furthermore, we provide evidence that this is driven through a neuroinflammatory mechanism independent of the mu-opioid receptor. It is well known that excessive neuroinflammation in brain regions such as the hippocampus can have deleterious consequences on neuronal structure & function which can ultimately undermine learning, memory, and cognition. In support of this, we found gene expression of synaptophysin and PSD95, two markers found in pre- and post-synaptic structures, respectively, to be significantly dysregulated in the hippocampus of aged, laparotomized, morphine-treated rats. Moreover, preliminary histological data suggests that dendritic spine density may also be altered in these animals. These data tentatively suggest that aging, surgery, and morphine may compromise neuronal structure and play a role in this persistent memory deficit. Altogether, this rat model closely mirrors the timeline of persistent POCD in humans; thus, providing insight into future treatments for patients suffering from POCD.
Keywords: Aging, Opioids, Neuroinflammation