Poster abstracts
Poster number 73 submitted by Lindsay Strehle
Microglia are implicated in brain region-specific tumor-induced neuroinflammation and behavioral comorbidities
Lindsay D. Strehle (Neuroscience Graduate Program; Institute for Behavioral Medicine Research), Corena V. Grant (Institute for Behavioral Medicine Research), Lauren Otto (Institute for Behavioral Medicine Research), Leah M. Pyter (Neuroscience; Psychiatry and Behavioral Health; Institute for Behavioral Medicine Research)
Abstract:
Breast cancer is the most common cancer among females worldwide. Following diagnosis, up to 30% of these patients report mood disturbances (i.e., anxiety, depression). Our tumor-bearing rodent model recapitulates the elevation of circulating inflammatory markers observed in cancer populations and displays concurrent increased proinflammatory mediators in the brain and negative affective-like behaviors. Neuroinflammation is a proposed mechanism behind the etiology of mood disorders and therefore may be contributing to these mood disturbances. However, the cellular mechanisms by which tumor-induced neuroinflammation occur remain unknown. We hypothesize that microglia are the primary cells driving tumor-induced neuroinflammation and therefore affective-like behaviors. We used young adult female Balb/c mice, half of which were induced with an orthotopic, syngeneic, non-metastatic 67NR mammary tumor; the other half underwent a sham surgery. Experiment 1 was designed to assess brain region-specific morphological (IHC) and gene expression activation of microglial cells (Ccl2, Il1b, Il6, Tnfa). Experiment 2 was designed to test the necessity of microglia in tumor-induced behavioral and neuroinflammatory outcomes using a colony stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) via chow. Remarkably, tumors did not alter the expression of primary microglia genes investigated relative to controls from Experiment 1. In the open field test of Experiment 2, tumor-bearing mice unexpectedly displayed greater entries and increased locomotion in the center of the field than tumor-free mice; these tumor-induced risky behaviors were attenuated by PLX5622 chow. Microglial depletion reversed tumor-induced increases in Il6 gene expression in the hippocampus without reducing peripheral inflammatory markers. These preliminary results suggest that microglia may have region- and mediator-specific involvement in tumor-induced neuroinflammation. IHC analyses are currently underway. This research will advance our understanding of the mechanisms underlying tumor-induced neuroinflammation and the associated behavioral deficits in order to identify specific cellular and/or molecular targets to mitigate cancer-associated behavioral comorbidities.
Keywords: mammary tumor, neuroinflammation, behavior