Journal of Neuroimmune Pharmacology

, Volume 7, Issue 1, pp 145–155

Behavioral, Structural and Molecular Changes following Long-term Hippocampal IL-1β Overexpression in Transgenic Mice

  • Amy M. Hein
  • Troy J. Zarcone
  • David B. Parfitt
  • Sarah B. Matousek
  • Dena M. Carbonari
  • John A. Olschowka
  • M. Kerry O’Banion
ORIGINAL ARTICLE

DOI: 10.1007/s11481-011-9294-3

Cite this article as:
Hein, A.M., Zarcone, T.J., Parfitt, D.B. et al. J Neuroimmune Pharmacol (2012) 7: 145. doi:10.1007/s11481-011-9294-3

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-1βXAT). 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-1βXAT 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.

Keywords

Interleukin-1βHippocampusNeuroinflammationLearningMemorySickness behavior

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Amy M. Hein
    • 1
  • Troy J. Zarcone
    • 2
  • David B. Parfitt
    • 3
  • Sarah B. Matousek
    • 4
  • Dena M. Carbonari
    • 1
  • John A. Olschowka
    • 1
  • M. Kerry O’Banion
    • 1
    • 5
  1. 1.Department of Neurobiology and AnatomyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  2. 2.National Institute on Alcohol Abuse and AlcoholismBethesdaUSA
  3. 3.State University of New YorkGeneseoUSA
  4. 4.Brigham and Women’s HospitalBostonUSA
  5. 5.University of Rochester Medical CenterRochesterUSA