Biobehavioral responses to immune skew and free fatty acids

Free fatty acid;Palmitic acid;Biobehavior;Macrophage;Immune skew;Anxiety

Moon, Morgan

关键词: Free fatty acid;    Palmitic acid;    Biobehavior;    Macrophage;    Immune skew;    Anxiety;   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/50343/Morgan_Moon.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

A well-described set of biobehaviors and cognitive dysfunction emerge after stimulation of the immune system with pathogen-associated or danger-associated molecular patterns, and the endogenous cytokines elaborated in the immunologic response are key effectors (Dantzer et al., 2008).Just as an organism’s response to a pathogen is defined by the host immune system status, so too is the basal cytokine environment altered by the endogenous immune skew (Gordon and Martinez, 2010).Shifting of cytokine skew has the capability to affect not only the immune and behavioral responses to exogenous stimuli, but to potentially alter biobehaviors observed in the naïve state (Moon et al., 2011).To test our hypothesis that skewing the immune system can alter biobehaviors exhibited in mice, we utilized two distinct models.In Chapter 2, the project of endogenous immune skew, interleukin-4 (IL-4) knock-out (KO) mice were behaviorally phenotyped.We have found that IL-4 KO animals display differences in burrowing, social exploration, elevated zero maze and the open field test, without any depressive-like behavior (forced swim test (FST), saccharin preference) or cognitive dysfunction (novel object recognition, novel object location, Morris water maze).In Chapter 3, the second project utilized a novel exogenous stimulus, palmitic acid (PA).We observed a dose-dependent decrease in home cage locomotion was noted two hours after PA treatment.This locomotor deficit was not dependent on canonical proinflammatory signaling pathways (Toll-like receptor 4, Myeloid differentiation primary response gene 88, interleukin-1 receptor 1, interleukin-6, Tumor necrosis factor α) and was not PA specific.After resolution of acute effects, PA treated animals displayed anxiety-like behavior (elevated zero maze, novel object investigation) but not depressive-like behavior (FST) or cognitive deficit (Y maze).Alterations to neurotransmitter balance in PA-treated mice were demonstrated in the amygdala and hippocampus.In conclusion, we demonstrated unique behavioral phenotypes in our endogenous immune skew and exogenous stimulus models.While these two approaches differed in some parameter responses, both models resulted in anxiety-like biobehaviors in mice.Taken together, these results suggest that a spectrum of effectors can lead to a common behavior.Further investigation is warranted to determine if and when common pathways for the observed behavior emerge, which could potentially lead to novel pharmaceutical treatment targets for anxiety and related psychopathologies.