However less is known about the role of dames à la recherche de jeunes villahermosa the broader network of cytokines in cognitive and annonce plan cul sans inscription affective regulation.
Here we aimed to determine (1) sex differences in broad networked activation of cytokines in the hippocampus, and (2) and differentia vulnerability of males and females to depression-like versus memory modulatory effects of systemic immune challenge.
Background: Systemic inflammation is associated with dysregulation of emotional states and cognitive function.
The differential vulnerabilities of males and females to mnemonic and affective modulation by immune stimulation are there likely to be due to which cytokines are present, and their kinetics of activation and resolution.Keywords: cytokine, neuroinflammation, Hippocampus, learning and memory, Depression.Conclusions: Together, these findings suggest that networked activity of cytokines in the brain, rather than individual cytokines, are central to vulnerability to cognitive and affective modulation.The CSF family also showed strong sex selectivity, with CSF1 and 2 only elevated in males, and CSF3 more strongly activated in females.Women are more vulnerable than men to the affective regulation of immune challenges, and this effect is often attributed to greater systemic immune responses compared with men.The sex-specific patterns of cytokine activity in the hippocampus were striking, with the IL-2 family (including IL-2, IL-15, and IL-4) upregulated in females, but not males.Rodent models mirror many of the effects of immune challenge and have demonstrated a clear role for IL-1, IL-6, and TNF in modulation of behavioral tasks.Second, males show a bias towards IFN-dependent signaling, whereas females show a shift towards IL-2, suggesting differential activation of astrocytes, microglia and neurons in the brain, and a role for the distinct downstream signaling pathways.Surprisingly, the strongest elevations in cytokine protein were not IL-1, IL-6, or TNF, but cxcl2, cxcl9 and 10, and the colony stimulating factor (CSF) family.Understanding how these sex-specific patterns of cytokine signaling contribute to vulnerability to cognitive and affective modulation will be critical for targeting dysregulation of neuroimmune signaling in disorders including depression and ptsd.Disclosures: Nothing to disclose.IL-13 and IL-4 are rapidly upregulated in females, whereas IL-13 and IL-10 are more slowly activated in males, providing one mechanism by which cytokine signaling may be shut off faster in females.The regulatory cytokines, IL-10, IL-13, and IL-4 are all activated in sex-biased manner.In contrast, IFN and IL-10 were only elevated in males.Methods: 9-11 Week old male and female C57Bl7/N mice (Harlan Laboratories) were housed individually in standard mouse caging, with ad lib access to food and water, a 12:12h light:dark cycle (lights on 7am-7pm) and maintained at 70F.More recent work, however, suggests that sex-specific activation of types of immune cells and patterns of cytokines, rather than magnitude of response per se, are more important determinants of outcome.
All procedures were approved by University of Michigan Animal Care and Use Committee.Plates were read on a MagPix (Luminex Corp) machine.In human studies, acute injection of lipopolysaccharide (LPS) to triggers inflammatory signaling and leads to changes in socio-emotional responses, and feelings of depression.In these data, several sex differences stand out.University of Michigan, Ann Arbor, Michigan, United States.In addition, despite growing evidence for sex-specific roles of immune cells in the brain, few studies have directly studied sex differences in central cytokine regulation and their modulation of affective and memory processes.Acute intraperitoneal (i.p) injections of lipopolysaccharide (LPS; E choli) at doses ranging from.5 - 250g/kg were administed prior to behavioral training (context fear conditioning, passive avoidance, forced swim test) or tissue dissection for cytokine analysis.Results: We demonstrated (a) broad network of activation of cytokines in the hippocampus, with strong, persistent activation of chemokines downstream of the rapidly activated IL-1, IL-6, IFN and TNF (b) qualitative and quantitative differences in cytokine profiles of males and females, as well as differential.The cytokines assayed were: CSF1, CSF2, CSF3, IL-1, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, IFN, cxcl1, cxcl2, cxcl5, cxcl9, cxcl10, CCL2, CCL3, CCL4, CCL5, CCL11, TNF, vegf, LIF, and LIX.Notably, increased circulating cytokine signaling, particularly interleukins -1 and - 6 (IL-1, IL-6) and tumor necrosis factor (TNF) may contribute to depression-like symptoms, cognitive impairments, and anxiety disorders including ptsd.
Statistical analysis used Multivariate anova and post-hoc tests with Scheffe correction for multiple comparisons.