Article

Chronic foot shock induces hyperactive behaviors and accompanying pro- and anti-inflammatory responses in mice.

Box PSYCH, Department of Psychiatry, University of Rochester, 300 Crittenden Blvd, Rochester, NY 14642, USA.
Journal of Neuroimmunology (Impact Factor: 2.79). 06/2007; 186(1-2):63-74. DOI: 10.1016/j.jneuroim.2007.03.003
Source: PubMed

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.

0 Followers
 · 
96 Views
  • Source
    • "Physical and psychological stress is a known risk factor for numerous human diseases, such as autoimmune diseases and cancer (Reiche et al., 2004; Shi et al., 2003; Cao et al., 2007; Frieri, 2003; Yang and Glaser, 2002). The immunological consequences of stress and the mechanisms by which stress compromises the immune system are important areas of study. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Physical and psychological stress can alter the immune system in both humans and animals. Stress is a known risk factor for numerous human diseases, such as infectious and autoimmune diseases, and cancer. Toll-like receptors (TLRs) play a pivotal role in the induction of innate and adaptive immune response. Our previous studies have shown that TLR4 deficiency prevents stress-induced splenocyte reduction. However, the role of TLR2 in stress-mediated lymphocyte reduction is unknown. In this study, we investigated the effects of TLR2 ligands on stress-induced lymphocyte reduction. We also defined whether the phosphoinositide 3-kinases (PI3Ks)/Akt pathway contributes to TLR2-mediated lymphocyte numbers altered by stress. Our data have shown that stimulation of TLR2 by TLR2 ligands peptidoglycan (PGN) or Pam3CSK4 (Pam3) attenuates stress-induced reduction in lymphocyte numbers. However, TLR2 ligand-induced protection from stress-induced lymphocyte reduction is lost in TLR2 deficiency in mice. Furthermore, stimulation of TLR2 by PGN induces protection from stress-induced reduction in the number of splenocytes through PI3K. Moreover, PGN dramatically increases the level of phosphorylation of Akt through a PI3K-dependent manner. Moreover, we found that stimulation of TLR2 by PGN induced protection from stress-induced reduction in splenocyte numbers is abolished in β-arrestin 2 deficient mice. In addition, PGN-induced immune protection in stress-induced changes of cytokine levels appears to require β-arrestin 2, a multifunctional adaptor and signal transducer. Collectively, our study thus demonstrates that stimulation of TLR2-mediated PI3K signaling attenuates splenocyte reduction induced by stress, and that β-arrestin 2 modulates TLR2-mediated immune response following stress.
    Journal of neuroimmunology 12/2010; 233(1-2):73-9. DOI:10.1016/j.jneuroim.2010.11.015 · 2.79 Impact Factor
  • Source
    • "Chronic stress or physiologically exhausting stress has significant suppressive effects on the immune system that includes innate and adaptive immunity, cell-mediated immunity and effector cell function (Reiche et al., 2004; Quan et al., 2001; Shi et al., 2003; Hawkley and Cacioppo, 2004). Stress is a known risk factor for numerous human diseases, such as infectious diseases, autoimmune diseases and cancer (Reiche et al., 2004; Shi et al., 2003; Dhabhar and McEwen, 1997; Cao et al., 2007). The cellular mechanisms underlying the suppressive effects of stress on the immune system have begun to be further understood as we have reported that physical restraint stress modulates the immune system through Toll-like receptors (TLRs) and the cell death receptor Fas-mediated apoptotic mechanism (Yin et al., 2000; Shi et al., 2003; Yin et al., 2006b; Zhang et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stress, either psychological or physical, can have a dramatic impact on the immune system. Toll-like receptors (TLRs) play a pivotal role in the induction of innate and adaptive immune response. We have reported that stress modulates the immune response in a TLR4-dependent manner. However, the mechanisms underlying TLR4-mediated signaling in stress modulation of immune system have not been identified. Here, we demonstrate an essential role for the TLR4-mediated phosphoinositide 3-kinase (PI3K)/Akt signaling. PI3K inhibition by inhibitors wortmannin or LY294002 abrogated protection of stress-induced immune suppression in TLR4-deficient mice compared with TLR4-deficient mice that did not receive the inhibitors. The mechanisms by which PI3K are increased in the TLR4-deficient lymphocytes may involve increased phosphorylation of Akt as well as increased phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta). The stress-mediated suppression of T help 1 (Th1) cytokine and increased production of Th2 cytokine was greatly reduced in TLR4 deficient mice compared with the wild type mice. Moreover, inhibition of PI3K diminished protection of the above Th1 and Th2 changes caused by stress in TLR4-deficient mice compared with non-stressed mice and the wild type mice. Our data demonstrated that TLR4 negatively regulates PI3K activity in wild type mice, leading to the observed the stress-induced immune response. The higher levels of PI3K prevent TLR4 deficient mice from the stress-induced immune response. Therefore, stress modulates the immune system through TLR4-mediated PI3K/Akt signaling.
    Journal of Neuroimmunology 10/2008; 204(1-2):13-9. DOI:10.1016/j.jneuroim.2008.08.011 · 2.79 Impact Factor
  • [Show abstract] [Hide abstract]
    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. DOI:10.1016/j.cbpc.2005.06.004 · 1.90 Impact Factor