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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Behavioral, structural and molecular changes following long-term hippocampal IL-1β overexpression in transgenic mice.

Authors: Hein, Amy M; Zarcone, Troy J; Parfitt, David B; Matousek, Sarah B; Carbonari, Dena M; Olschowka, John A; O'Banion, M Kerry

Published In J Neuroimmune Pharmacol, (2012 Mar)

Abstract: Chronic neuroinflammation is associated with many neurodegenerative and neurocognitive disorders, yet few animal models exist to study the behavioral effects of prolonged neuroinflammation. Therefore, we recently developed a transgenic mouse model harboring an interleukin-1β excisional activation transgene (IL-1β(XAT)). These mice display localized IL-1β overexpression and resultant neuroinflammation for up to 1 year following transgene induction. Initial behavioral studies demonstrated long-term memory deficits after 2 weeks of hippocampal IL-1β overexpression. In the present studies, we extend these behavioral studies both in scope and timing. We find long-term contextual but not auditory fear memory impairments following 3 months of IL-1β overexpression. On a battery of other behavioral tests, IL-1β overexpression in IL-1β(XAT) mice increased locomotor activity, especially in female mice, and had slight anxiolytic effects. No differences were found in operant conditioning or in basal or stress-induced CORT levels, despite profound hippocampal glial activation. Interestingly, the volume of discrete hippocampal cell layers was reduced after 6 but not 3 months of IL-1β overexpression. Therefore, this animal model provides a novel tool for examining the effects of chronic inflammation on discrete brain regions.

PubMed ID: 21748283 Exiting the NIEHS site

MeSH Terms: Animals; Behavior, Animal/physiology; Female; Hippocampus/immunology*; Hippocampus/metabolism*; Hippocampus/pathology*; Immunohistochemistry; Inflammation/immunology*; Inflammation/metabolism; Interleukin-1beta/biosynthesis; Interleukin-1beta/immunology*; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation

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