![]() Paul Phillips*, Nick Hollon, Monica Arnold, Vicente Martinez, Mark Walton University of Washington, Seattle, Washingtonīackground: Contemporary theories of reward-based decision making posit that dopamine signaling updates cached values associated with stimuli or actions and that these values are used to compare available options in making choices. Keywords: Depression, cytokine, micro-array, mouse. Comparing these results with transcriptional changes in humans may help elucidate why most people don’t develop depression in the setting of inflammation and why some do. This includes members such as MAPKKK3 and protein kinase C-delta, whose activation can trigger MAPK phosphatase degradation and thus increase activation of the MAPK/ERK pathway. Interestingly, anhedonia was most associated with transcripts regulated by HRas. IFN-α only has subtle behavioral effects in mice. Many of brain transcripts likely reflect microglial activation. Transcripts changes that most correlated with anhedonic-like behaviors were those regulated by HRas (p=7x10-7), which is a small GTPase that can activate Raf kinase, and subsequently the MAPK/ERK pathway.Ĭonclusions: Importantly for human studies, many of the IFN-induced transcripts in the brain are also influenced in the peripheral blood. The transcripts increased in both FC and AMY are known to be influenced by IFN-α receptor signaling (p=4.4 x 10-24) and normally inhibited by TRIM24 (p=2.6 x10-16). Of the 57 increased in both FC and amygdala (AMY), 55 were also increased in the blood. Of the 95 transcripts increased by IFN-α in the frontal cortex (FC), 70 were also increased in the blood. There was only a trend for increased anhedonic-like behaviors with IFN-α. Results: Four behavioral factors were obtained, only one of which differed between vehicle and IFN-α. With Ingenuity Canonical Pathway analyses, we explored associations of transcripts with behavior. Differential expression was determined using LIMMA. ![]() After three weeks of daily injections, RNA from punch biopsies of brain tissue (frontal cortex/amygdala) and blood samples were then obtained and examined using Illumina microarrays. Behavioral results were collated using principal component analyses. Methods: Male BALB/c mice (n=32) were given daily injections of either vehicle or IFN-α, and then assessed for behavioral alterations from day 14-21 using the following tests: elevated plus-maze, open-field, novelty suppressed feeding, self-grooming following a spray test, cookie test, a two-bottle sucrose choice test, and a forced swimming test. We examined whether there would be similar variability in the behavioral effects of IFN-α in mice, and then explored associations between behavior and changes in gene transcription. However, only some individuals are vulnerable to this effect ( ∼25%), with most being resilient. Many depression symptoms typically take several weeks to develop. Francis Lotrich*, Beverly French, Charles Ma, Marianne Seney, Etienne Sibille, George Tseng Western Psychiatric Institute & Clinic, Pittsburgh, Pennsylvaniaīackground: Inflammatory cytokines, including interferon-alpha (IFN-α), are known to precipitate depression symptoms in humans.
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