Date of Degree
Susan D. Croll
aging; anxiety; cognition; depression; Interleukin-1; sex differences
IL1-R1 null mutant mice (IL1-R1 KO) have reduced signaling in the interleukin-1 (IL-1) pathway, making them a convenient model for testing the importance of IL-1 in either the development or maintenance of mouse behaviors. Prior research has revealed impaired cognitive and emotional processes in adult male IL1-R1 KO mice, including impaired spatial learning and memory and decreased anxiety with associated impairments in hippocampal cell proliferation and signal transmission. The current studies explored the neuroanatomy and behavioral phenotype of both male and female IL1-R1 KO mice. An array of behavioral tests was administered, including retesting at an older age for cognitive and emotional behaviors. Animals were sacrificed and their brains were measured for neuroanatomical abnormalities, cell population densities, and vascular proliferation. The results were consistent with prior findings of impaired spatial learning and memory performance for male IL1-R1 KO animals, as well as reduced anxiety-type responses in multiple behavioral tests. Female IL1-R1 KO mice were less affected, and showed no behavioral impairment in the Morris Water Maze (MWM). The findings also revealed an increased depressive-type behavior in the Porsolt Forced-Swim test (FST), but only in female IL1-R1 KO animals. All animals were retested at a later age in the MWM to determine if the observed sex-based differences in impaired spatial learning and memory would persist or increase with age. We found impaired spatial memory performance for aged IL1-R1 KO animals, and although older male KOs showed poorer performance in the MWM than female KOs, the difference between sexes no longer achieved statistical significance. Neuroanatomical evaluation revealed no gross differences in cortical or hippocampal structure. However, IL1-R1 KO animals had significantly reduced vascular investment in the hippocampal region, a finding that significantly correlated with impaired spatial memory performance in older animals. These findings suggest that disruption of normal IL-1 activity can influence vascular density in the hippocampus and also alter hippocampally-mediated behavior, including spatial learning and memory. The findings also reveal sex-dependency of these effects, suggesting the possibility that male and female animals suffer different behavioral consequences of IL-1 signaling deficiency.
Johnson, Jennifer Anne, "Sex-dependent Role of Interleukin-1 Signaling in Emotional and Cognitive Behaviors in Mice: Phenotyping Male and Female IL1-R1 Null Mutant Mice" (2015). CUNY Academic Works.