The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia

O’Connor, Terence M.; O’Halloran, Domhnall J; Shanahan, Fergus

doi:10.1093/qjmed/93.6.323

Cited by 325 publications

(255 citation statements)

References 85 publications

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“…However, in the present study, the hematology analyzer was used showing that the number of WBC and the percentage of granulocytes (eosinophils + basophils) decreased significantly in heat-stressed pigs. These findings are in accordance with a previous study in which the percentages of basophils and eosinophils, leukocytes and monocytes were reduced by glucocorticoids in stressed animals (O'Connor et al, 2000). This inhibition is mediated at the level of cytokine gene transcription, and by inhibition of the production of arachidonic acid-derived proinflammatory substances (Panes et al, 2009).…”

Section: Discussionsupporting

confidence: 93%

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Yong

et al. 2014

Animal

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Global warming is a challenge to animal health, because of increased heat stress, with subsequent induction of immunosuppression and increased susceptibility to disease. Toll-like receptors (TLR) are pattern recognition receptors that act as sentinels of pathogen invasion and tissue damage. Ligation of TLRs results in a signaling cascade and production of inflammatory cytokines, which eradicate pathogens and maintain the health of the host. We hypothesized that the TLR signaling pathway plays a role in immunosuppression in heat-stressed pigs. We explored the changes in the expression of TLR2, TLR4 and the concentration of acute inflammatory cytokines, such as IL-2, IL-8, IL-12 and IFN-γ in Bama miniature pigs subjected to 21 consecutive days of heat stress, both in vitro and in vivo models. The results showed that heat stress induced the upregulation of cortisol in the plasma of pigs (P < 0.05); TLR4 mRNA was elevated, but IL-2 was reduced in peripheral blood mononuclear cells (PBMC, P < 0.05). The white blood cell count and the percentage of granulocytes (eosinophilic + basophilic) decreased significantly in heat-stressed pigs (P < 0.05). In the in vitro model (PBMC heat shocked for 1 h followed by a 9 h recovery period), TLR2 and TLR4 mRNA expression also increased, as did the concentration of IL-12 in supernatants. However, IFN-γ was significantly reduced in PBMC culture supernatants (P < 0.05). We concluded that a consecutive heat stress period elevated the expression of TLR2 and TLR4 in PBMC and increased the plasma levels of inflammatory cytokines. These data indicate that TLR activation and dysregulation of cytokine expression in response to prolonged heat stress may be associated with immunosuppression and increased susceptibility to antigenic challenge in Bama miniature pigs.

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Section: Discussionsupporting

confidence: 93%

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Yong

et al. 2014

Animal

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“…As noted earlier, the ultimate function of PTX3 is unknown, although it is associated with neuronal apoptosis and may have a neuroprotective role (Ravizza et al, 2001). If the increased expression of PTX3 is confirmed in the brains of patients with depression, the finding will add to a growing body of evidence, suggesting neuroendocrineimmune dysfunction in melancholia (Miller et al, 1999;O'Connor et al, 2000).…”

Section: Discussionmentioning

confidence: 87%

Differential Expression of Pentraxin 3 in Fibroblasts from Patients with Major Depression

Shelton

Shan

Peng

et al. 2003

Neuropsychopharmacol

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In this study, differential display technology was used to compare gene expression in cultured fibroblasts from patients with major depression, melancholic subtype vs nonmelancholic depressives and normal volunteer controls. Genes differentially expressed in depressives and normals included an overexpressed 269 bp sequence tag showing B95% identity with the Homo sapiens long pentraxin 3 (PTX3) gene sequence in the 3 0 noncoding region. The 269 bp complimentary DNA probe hybridized with the 1.9 kb PTX3 mRNA. The densitometric analysis of slot blots showed that the mean steady-state mRNA level of PTX3 was 3.5-fold higher in the melancholic group as compared to that in normal controls and in nonmelancholic depressives (n ¼ 8, all groups). Incubation experiments were then conducted: confluent fibroblasts from melancholics and normal volunteers were incubated with isoproterenol 1 mM, dexamethasone (DEX) 500 nM, and interleukin 1b (IL-1b) 50 ng/ml, for 0, 0.5, 1, 4, and 24 h. mRNA was isolated and quantitated using Northern blot analysis. Isoproterenol produced no significant change in PTX3 expression; DEX produced a significant increase at 4 and 24 h; IL-1b induced an increase in both the groups that peaked at 4 h, declining to near basal levels at 24 h. There were no differences between melancholics or controls in mean change or maximum response with either DEX or IL-1b. The results are consistent with the reported effects of IL-1b on PTX3 expression in mouse brain. The results are of potential importance because PTX3 is a member of the long pentraxin subfamily of acute-phase proteins, which is inducible by IL-1b, and may play roles in neuroimmunity and neuroprotection.

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“…Activation of the locus coeruleus (LC)-norepinephrine (NE) system is a consistent response to stress that may function to optimize the state of arousal and mode of attention for adaptation to the challenge (Chrousos and Gold, 1992;O'Connor et al, 2000;Leonard, 2001;Vermetten and Bremner, 2002;Berridge and Waterhouse, 2003;Valentino and Van Bockstaele, 2005). As these functions are disrupted in depression and depression responds to agents that modulate brain NE activity, the LC-NE system is another potential substrate for sex differences in stress-related disorders.…”

Section: Introductionmentioning

confidence: 99%

Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

Curtis

Bethea

Valentino

2005

Neuropsychopharmacol

192

196

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Stress-related psychiatric disorders are more prevalent in females than males, and this has been attributed to differences in stress sensitivity. As activation of the locus coeruleus (LC)-norepinephrine (NE) system is an important component of the stress response, this study compared LC responses to stress in female and male rats under different hormonal conditions in the halothane-anesthetized state. The mean basal LC discharge rate was similar between groups. However, the magnitude of LC activation elicited by hypotensive stress was substantially greater in females, regardless of hormonal status. The difference in stress sensitivity could be attributed to the differential postsynaptic sensitivity of LC neurons to corticotropin-releasing factor (CRF), which mediates LC activation by hypotension. CRF was 10-30 times more potent in activating LC neurons in female vs male rats. Interestingly, previous exposure to swim stress differentially regulated LC responses to CRF by sensitizing LC neurons of male, but not female, rats to CRF. The net effect of this was to abolish sex differences in LC sensitivity. Finally, CRF receptor (CRF-R) protein levels in the LC were greater in ovarectomized female vs male rats. This is the first study to demonstrate sex differences in the stress responsiveness of the brain noradrenergic system. Substantial sex differences were apparent in postsynaptic sensitivity to CRF and stress-induced regulation of postsynaptic sensitivity to CRF. These sex differences in the CRF regulation of the LC-NE system translate to a differential response to stress and may play a role in the increased vulnerability of females to stress-related psychiatric disorders.

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The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia

Cited by 325 publications

References 85 publications

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Heat stress upregulation of Toll-like receptors 2/4 and acute inflammatory cytokines in peripheral blood mononuclear cell (PBMC) of Bama miniature pigs: an in vivo and in vitro study

Differential Expression of Pentraxin 3 in Fibroblasts from Patients with Major Depression

Sexually Dimorphic Responses of the Brain Norepinephrine System to Stress and Corticotropin-Releasing Factor

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