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

Authors

  • Amy M. Hein
    • Department of Neurobiology and AnatomyUniversity of Rochester School of Medicine and Dentistry
  • Troy J. Zarcone
    • National Institute on Alcohol Abuse and Alcoholism
  • David B. Parfitt
    • State University of New York
  • Sarah B. Matousek
    • Brigham and Women’s Hospital
  • Dena M. Carbonari
    • Department of Neurobiology and AnatomyUniversity of Rochester School of Medicine and Dentistry
  • John A. Olschowka
    • Department of Neurobiology and AnatomyUniversity of Rochester School of Medicine and Dentistry
    • Department of Neurobiology and AnatomyUniversity of Rochester School of Medicine and Dentistry
    • University of Rochester Medical Center
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