title: Behavioral, structural and molecular changes following long-term hippocampal IL-1β overexpression in transgenic mice.
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.
authors: Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
authors: Amy M
authors: AM
authors: Hein
authors: Troy J
authors: TJ
authors: Zarcone
authors: David B
authors: DB
authors: Parfitt
authors: Sarah B
authors: SB
authors: Matousek
authors: Dean M
authors: DM
authors: Carbonari
authors: John A
authors: JA
authors: Olschowka
authors: M Kerry
authors: MK
authors: O'Banion
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D053583:Interleukin-1beta