title: Interleukin-1β causes long-term potentiation deficiency in a mouse model of septic encephalopathy.
abstract: Sepsis induces multiple organ dysfunction syndrome including septic encephalopathy (SE), which results in cognitive impairment. However, an effective treatment for SE remains unknown. We determined the role of interleukin-1β (IL-1β) in long-term potentiation (LTP) deficiency after SE. At first, endotoxin level in the blood was increased at 24 h after cecum ligation and puncture (CLP) (i.e. SE model). Second, the expression of IL-1β and its receptor in the hippocampus was determined by immunohistochemistry and immunoblotting. The number of Iba1-positive cells and their expression of IL-1β were enhanced by CLP with disruption of the blood brain barrier. Also, Iba1, IL-1β, and occludin protein expressions were consistent with immunohistochemical results. Third, we used an electrophysiological technique and observed the LTP deficiency, a hallmark of learning and memory, in the slices of hippocampus after CLP. Since type 1 interleukin-1 receptors (IL-1R1s) on neuronal cells were increased in the hippocampus, we utilized IL-1R1 antagonist. Pre-incubation with IL-1R1 antagonist for 30 min before recording of field excitatory post-synaptic potentials (fEPSPs) in the hippocampus canceled LTP deficiency after CLP. These results suggest the novel importance of IL-1β in synaptic plasticity deficiency associated with sepsis-induced brain inflammation. In a mouse model of SE, IL-1R1 inhibition is important in protecting synaptic function of the hippocampus after induction of SE.
authors.affiliation: Department of Trauma and Acute Critical Care Center, Osaka University Hospital, Osaka, Japan. yimamura-ns@umin.net
authors.forename: Y
authors.initials: Y
authors.lastname: Imamura
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: N
authors.initials: N
authors.lastname: Matsumoto
authors.forename: T
authors.initials: T
authors.lastname: Muroya
authors.forename: J
authors.initials: J
authors.lastname: Shimazaki
authors.forename: H
authors.initials: H
authors.lastname: Ogura
authors.forename: T
authors.initials: T
authors.lastname: Shimazu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1