Postoperative cognitive dysfunction is made persistent with morphine treatment in aged rats.

Autor: Muscat SM; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Biomedical Sciences Graduate Program, The Ohio State University, Columbus, OH, USA., Deems NP; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Neuroscience Graduate Program, The Ohio State University, Columbus, OH, USA., D'Angelo H; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Kitt MM; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Grace PM; Laboratories of Neuroimmunology, Department of Symptom Research, University of Texas MD Anderson Cancer Center, Houston, TX, USA., Andersen ND; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Silverman SN; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Rice KC; Drug Design and Synthesis Section, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA., Watkins LR; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Maier SF; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA., Barrientos RM; Institute for Behavioral Medicine Research, The Ohio State University, Columbus, OH, USA; Department of Psychology and Neuroscience, Center for Neuroscience, University of Colorado Boulder, Boulder, CO, USA; Department of Psychiatry and Behavioral Health, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA; Chronic Brain Injury Program, Discovery Themes Initiative, The Ohio State University, Columbus, OH, USA. Electronic address: ruth.barrientos@osumc.edu.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2021 Feb; Vol. 98, pp. 214-224. Date of Electronic Publication: 2020 Nov 24.
DOI: 10.1016/j.neurobiolaging.2020.11.008
Abstrakt: Postoperative cognitive dysfunction (POCD) is the collection of cognitive impairments, lasting days to months, experienced by individuals following surgery. Persistent POCD is most commonly experienced by older individuals and is associated with a greater vulnerability to developing Alzheimer's disease, but the underlying mechanisms are not known. It is known that laparotomy (exploratory abdominal surgery) in aged rats produces memory impairments for 4 days. Here we report that postsurgical treatment with morphine extends this deficit to at least 2 months while having no effects in the absence of surgery. Indeed, hippocampal-dependent long-term memory was impaired 2, 4, and 8 weeks postsurgery only in aged, morphine-treated rats. Short-term memory remained intact. Morphine is known to have analgesic effects via μ-opioid receptor activation and neuroinflammatory effects through Toll-like receptor 4 activation. Here we demonstrate that persistent memory deficits were mediated independently of the μ-opioid receptor, suggesting that they were evoked through a neuroinflammatory mechanism and unrelated to pain modulation. In support of this, aged, laparotomized, and morphine-treated rats exhibited increased gene expression of various proinflammatory markers (IL-1β, IL-6, TNFα, NLRP3, HMGB1, TLR2, and TLR4) in the hippocampus at the 2-week time point. Furthermore, central blockade of IL-1β signaling with the specific IL-1 receptor antagonist (IL-1RA), at the time of surgery, completely prevented the memory impairment. Finally, synaptophysin and PSD95 gene expression were significantly dysregulated in the hippocampus of aged, laparotomized, morphine-treated rats, suggesting that impaired synaptic structure and/or function may play a key role in this persistent deficit. This instance of long-term memory impairment following surgery closely mirrors the timeline of persistent POCD in humans and may be useful for future treatment discoveries.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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