Volume 67, January 2018, Pages 355-363
Author links open overlay panelMeghan E.JonesChristina L.LebonvilleJacqueline E.PanicciaMegan E.BalentineKathryn J.ReissnerDonald T.LysleUniversity of North Carolina at Chapel Hill, Department of Psychology and Neuroscience, United States
•Blocking DH stress-induced IL-1 signaling prevents stress-enhanced fear learning.
•Hippocampal Iba-1, but not GFAP, is attenuated 48 h after stress exposure.
•Stress-induced hippocampal IL-1β is colocalized primarily with GFAP.
Post-traumatic stress disorder (PTSD) is associated with immune dysregulation. We have previously shown that severe stress exposure in a preclinical animal model of the disorder, stress-enhanced fear learning (SEFL), is associated with an increase in hippocampal interleukin-1β (IL-1β) and that blocking central IL-1 after the severe stress prevents the development of SEFL. Here, we tested whether blocking hippocampal IL-1 signaling is sufficient to prevent enhanced fear learning and identified the cellular source of stress-induced IL-1β in this region. Experiment 1 tested whether intra-dorsal hippocampal (DH) infusions of interleukin-1 receptor antagonist (IL-1RA, 1.25 µg per hemisphere) 24 and 48 h after stress exposure prevents the development of enhanced fear learning. Experiment 2 used triple fluorescence immunohistochemistry to examine hippocampal alterations in IL-1β, glial fibrillary acidic protein (GFAP), an astrocyte-specific marker, and ionized calcium binding adaptor molecule -1 (Iba-1), a microglial-specific marker, 48 h after exposure to the severe stressor of the SEFL paradigm. Intra-DH IL-1RA prevented SEFL and stress-induced IL-1β was primarily colocalized with astrocytes in the hippocampus. Further, hippocampal GFAP immunoreactivity was not altered, whereas hippocampal Iba-1 immunoreactivity was significantly attenuated following severe stress. These data suggest that hippocampal IL-1 signaling is critical to the development of SEFL and that astrocytes are a predominant source of stress-induced IL-1β.