Chronic foot shock induces hyperactive behaviors and accompanying pro- and anti-inflammatory responses in mice.
ABSTRACT Behavioral and accompanying physiological and immunological changes were investigated at various times during chronic irregular mild foot shock (CMFS) in adult male BALB/c mice. CMFS induced a significant hyperlocomotor activity in a familiar environment as well as increased consumption of chocolate milk (a favored drink) throughout the 5-week stress period. Unlike other chronic stress models, CMFS did not induce depressive-like behaviors. Hyperactivity was associated with transient elevations of pro-inflammatory cytokines (TNFalpha and IL-1beta) and IL-2 and more sustained (IL-10) or later (arginase activity) elevations in anti-inflammatory mediators in the spleen (serum levels below levels of detection) suggesting a transition from a pro-inflammatory state to an anti-inflammatory state during CMFS. Similar increases in brain levels of IL-2 and arginase activity were also detected and may contribute to CMFS-induced hyperactivity as both of these mediators have been shown to induce hyperactivity. To our knowledge, this is the first time that increased arginase activity has been documented during a stress paradigm. Altogether, the data indicate that CMFS induces behavioral changes distinct from other chronic stress models. CMFS is associated with multiple dynamic immunological changes, suggesting involvement of multiple factors in chronic stress-induced behavioral changes.
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ABSTRACT: We describe a simple and effective procedure to isolate antifreeze proteins (AFPs) from the hemolymph of larvae of the longhorn beetle Rhagium inquisitor, and present some characteristics of their structures. Several AFPs were isolated from the hemolymph of this species by heat and acid extraction followed by cation exchange. The hemolymph contains at least six AFPs ranging in size from 12.5 to 12.8 kDa. Of these, three were separated to purity by the ion exchange step, as indicated by mass spectrometry. The remaining three forms were further separated by size exclusion chromatography, but could not be isolated to purity. All AFPs in the hemolymph of this species appears to have isoelectric points above 8.00. The dominant form, RiAFP(H4), was purified by the ion exchange step. Its amino acid composition reveals a lower level of cysteine and a higher level of threonine, arginine, alanine and glycine than seen in other insect AFPs. Its trypsin fingerprint does not match that of any known protein. It interacts with ice both in the anionic and cationic state.Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology 10/2005; 142(1):90-7. · 2.07 Impact Factor
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ABSTRACT: OBJECTIVE: To investigate the relationship between emotional status, cold-dry environment and long-term immune responses to the stressors, and the potential pathological mechanisms between causative factors of abnormal Savda syndrome (ASS) and the susceptibility to disease; thus to clarify the ASS, and secondly to identify the optimal ASS animal model for further studies on traditional Uighur therapeutical formulations. METHODS: Sixty mice were randomly and equally divided into 4 groups: control and 3 stress groups. The cold-dry environment was applied by keeping the mice in a climatic chamber. The emotional stress was induced by the application of the repeated electric foot-shocks in the electric foot-shock apparatus. The mice of the combined stress group underwent the repeated electric foot-shock treatment before being housed in the climatic chamber. The experimental routine was repeated for 21 days. In order to look into endocrine and immune stress responses, ELISA was used to determine the serum levels of the hormones corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), Beta-endorphin (β-END) and corticosterone (CORT), of the cytokines interleukin 2 (IL-2), interleukin 6 (IL-6), interferon-gamma (INF-γ) and tumor necrosis factor-alpha (TNF-α), and of the immunoglobulins immunoglobulin A (IgA), immunoglobulin M (IgM) and immunoglobulin G (IgG). Lymphocyte subsets were analyzed in duplicate in order to determine differences in the T cell ratio. RESULTS: In the cold-dry environment group, the serum levels of CRH, ACTH and CORT were significantly higher than those of the control group, whereas serum β-END was not found significantly different. In both the repeated electric foot-shock group as well as in the combined stress group the serum levels of CRH, ACTH, β-END and CORT were significantly higher. Compared to the control animals, the serum concentration of INF-γ was significantly lower in all three different stress groups. The serum level of IL-2 was decreased in the combined stress group whereas the serum TNF-α level was significantly higher. The serum IgG level was significantly higher in all three stress groups, whereas the IgA level was lower in both chronic electric foot-shock group and combined stress group. The IgM level was found significantly higher in the combined stress group only. The percentage of CD4(+) cells in peripheral blood was dramatically decreased in mice exposed to colddry environment, chronic electric foot-shock and combined stress, whereas the percentage of the CD8(+) subset was not significantly different. The CD4(+)/CD8(+) ratios were markedly lower in both cold-dry environment group and combined stress group. CONCLUSIONS: Combined stress can cause hyperactivity of the HPA axis, and an imbalance in the Th1/Th2 cell subset may contribute to illustrate the partial pathological mechanisms of ASS. This study identified this animal model of a combination of physical and emotional stress as an optimal model for further studies on ASS and relative therapies.Chinese Journal of Integrative Medicine 05/2012; · 1.06 Impact Factor
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ABSTRACT: Stress, either physical or psychological, can modulate immune function. However, the mechanisms associated with stress-induced immune suppression remain to be elucidated. β-Arrestin 2 serves as adaptor, scaffold, and/or signal transducer. The role of β-arrestin 2 in stress-induced immune suppression is not known yet. Here, we demonstrate that β-arrestin 2 deficiency in mice increases the sensitivity to the chronic stress-induced reduction in the number of splenocytes. Interestingly, the stress-induced suppression of T helper-type (Th) 1 cytokines and the increased production of Th2 cytokines were greatly enhanced in β-arrestin 2-deficient mice compared with wild-type mice. Moreover, inhibition of PI3K in β-arrestin 2-deficient mice exerts an additive effect on the stress-induced reduction in the number of splenocytes. Our study demonstrates that a deficiency in β-arrestin 2 augments stress-induced immune suppression.NeuroImmunoModulation 01/2011; 18(3):142-9. · 1.84 Impact Factor