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.
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Acknowledgements
We would like to thank S. Kyrkanides and J. Miller for FIV packaging, M. Olschowka and J. Walter for animal colony management, and L. Trojancyzk for help with tissue processing. The present work was supported by NIH RO1 AG030149 andP30 ES001247. A. Hein was supported by an NINDS T32 training grant in neuroinflammation and glial cell biology (NIH T32 NS051152).
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Guarantors: Amy Hein and M. Kerry O’Banion
Funding: NIH RO1 AG030149, P30 ES001247, and T32 NS051152.
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Hein, A.M., Zarcone, T.J., Parfitt, D.B. et al. Behavioral, Structural and Molecular Changes following Long-term Hippocampal IL-1β Overexpression in Transgenic Mice. J Neuroimmune Pharmacol 7, 145–155 (2012). https://doi.org/10.1007/s11481-011-9294-3
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DOI: https://doi.org/10.1007/s11481-011-9294-3