title: Acute systemic LPS-mediated inflammation induces lasting changes in mouse cortical neuromodulation and behavior.
abstract: Systemic lipopolysaccharide (LPS) is widely used to induce a neuroinflammatory response that is associated with short-term 'sickness'-behavior that can include fever, loss of activity, loss of appetite, impaired cognition, anxiety and depression. If large enough or left unchecked, this neuroinflammatory response can become self-perpetuating and lead to long-term neurodegenerative processes. In this study, we assess the longer-term effects of a single systemic LPS injection on electrophysiological neuromodulator effects and basic behavioral analysis in mice. Five months after LPS injection, we find a mild reduction in cortical inhibition and altered temporal dynamics of acetylcholine but not norepinephrine or serotonin neuromodulator effects. Consistent with electrophysiological findings, LPS treated mice showed a deficit in memory performance in the novel object recognition test with no effect on measures of anxiety or despair as measured in the open field test and tail suspension test, respectively. Furthermore, LPS-treated mice showed an increase in acetylcholinesterase activity. As increased acetylcholinesterase activity is associated with reduced acetylcholine signaling and impaired cognitive ability, these studies demonstrate the potential for a single inflammatory event to initiate processes that may lead to long-term neurodegeneration.
authors: Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7 N 5E5, Canada.
authors: Z
authors: Z
authors: Ming
authors: Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7 N 5E5, Canada; Department of Clinical Chemistry, Medical University of Wroclaw, Wroclaw 50-556, Poland.
authors: G
authors: G
authors: Sawicki
authors: Department of Pharmacology, University of Saskatchewan, Saskatoon, SK S7 N 5E5, Canada. Electronic address: lane.bekar@usask.ca.
authors: L K
authors: LK
authors: Bekar
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000523:psychology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003071:Cognition / Q000187:drug effects*; D005106:Exploratory Behavior; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D013315:Stress, Psychological / Q000523:psychology
chemical_list: D008070:Lipopolysaccharides; D018377:Neurotransmitter Agents; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase; D000109:Acetylcholine
keywords: Cortical inhibition; Cortical network; Memory; Phasic neuromodulator release