Chronic Restraint Stress Upregulates Erythropoiesis through Glucocorticoid Stimulation

Voorhees, Jeffrey L.; Powell, Nicole D.; Moldovan, Leni; Mo, Xiaokui; Eubank, Timothy D.; Marsh, Clay B.

doi:10.1371/journal.pone.0077935

Cited by 29 publications

(21 citation statements)

References 53 publications

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“…Irrespective of AVP deficiency, patients with cDI generally have other factors influencing haematopoiesis, for example anterior pituitary deficiency with or without replacement therapy. Although there is evidence that thyroid hormones 18,19 and glucocorticosteroids 20‐22 have an impact on erythropoiesis, we did not find any association of hypothalamic‐pituitary‐thyroid hormone or HPA axis deficiency and altered haemoglobin levels in cDI patients. This is most likely explained by the euthyroid and euadrenal state of our patients under replacement therapy.…”

Section: Discussioncontrasting

confidence: 92%

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia

Winzeler

Morin

Refardt

et al. 2020

Clinical Endocrinology

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Objective Arginine vasopressin (AVP) is released upon osmotic stimulation or hypovolaemia in order to maintain water balance. A recent study showed a role of AVP in haematopoiesis by stimulating red blood cell precursors, suggesting a higher risk of anaemia in patients with AVP deficiency. The objective was to explore the effect of low AVP levels in patients with central diabetes insipidus (cDI) and primary polydipsia (PP) on haemoglobin and the prevalence of anaemia. Methods A total of 164 patients with either cDI (70, 43%) or PP (94, 57%) and 30 healthy volunteers from two prospective diagnostic studies performed in Switzerland, Germany and Brazil were studied. A standardized clinical and biochemical (eg copeptin, full blood count) assessment was performed. Haemoglobin and haematocrit levels and prevalence of anaemia (defined as haemoglobin values of <120 g/L in women and <130 g/L in men) were analysed. Results Mean copeptin values were 2.63 pmol/L (±1.08) and 3.91 pmol/L (±4.28) in patients with cDI and PP and 24.76 pmol/L (±5.75) in healthy volunteers, P = .02. The prevalence of anaemia was low in all participants with 7.1%, 2.2% and 10% in cDI, PP and in healthy volunteers, P = .15. Mean haemoglobin values were similar in all groups: 139 g/L (±15.85), 140 g/L (±13.16) and 139 g/L (±13.05) in patients with cDI, PP and healthy volunteers, P = .90, as were mean haematocrit values with 41% in all groups (P = .85). Conclusion Chronic low AVP levels in patients with cDI and PP do not affect haemoglobin levels and prevalence of anaemia.

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Section: Discussioncontrasting

confidence: 92%

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia

Winzeler

Morin

Refardt

et al. 2020

Clinical Endocrinology

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“…The CRS model is known to induce psychological stress and is often used to study depression [ 37 , 38 ]. Although diverse factors contribute to the development of depression, recent research has suggested that neuroinflammation has a significant role in the pathogenesis of depressive disorders [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates depressive-like behavior in a mouse model of chronic stress

Zhao

Pan

et al. 2017

J Neuroinflammation

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BackgroundIt has been shown that chronic stress-induced depression is associated with exaggerated inflammatory response in the brain. Alpha7 nicotinic acetylcholine receptors (α7nAChRs) regulate the cholinergic anti-inflammatory pathway, but the role of cholinergic signaling and α7nAChR in chronic stress has not yet been examined.MethodsIn this study, we used a well-documented model of depression in which mice were exposed to 6 h of restraint stress for 21 consecutive days. Components of cholinergic signaling and TLR4 signaling were analyzed in the hippocampus. The main targets of neuroinflammation and neuronal damage were also evaluated after a series of tests for depression-like behavior.ResultsChronic restraint stress (CRS) induced alterations in components of central cholinergic signaling in hippocampus, including increases in choline acetyltransferase protein expression and decreases in nuclear STAT3 signaling. CRS also increased TLR4 signaling activity, interleukin-1β, and tumor necrosis factor-α expression, microglial activation, and neuronal morphologic changes. Cholinergic stimulation with the α7nAChR agonist DMXBA significantly alleviated CRS-induced depressive-like behavior, neuroinflammation, and neuronal damage, but these effects were abolished by the selective α7nAChR antagonist α-bungarotoxin. Furthermore, activation of α7nAChRs restored the central cholinergic signaling function, inhibited TLR4-mediated inflammatory signaling and microglial activity, and increased the number of regulatory T cells in the hippocampus.ConclusionsThese findings provide evidence that α7nAChR activation mitigates CRS-induced neuroinflammation and cell death, suggesting that α7nAChRs could be a new therapeutic target for the prevention and treatment of depression.Electronic supplementary materialThe online version of this article (10.1186/s12974-017-1007-2) contains supplementary material, which is available to authorized users.

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“…The increase in serum levels of corticosterone in the disharmony group exceeded the 200 ng/ml threshold considered to reflect ‘stress’ in rodents (Fig. 2 ) 3 , 18 .…”

Section: Discussionmentioning

confidence: 81%

Occlusal disharmony-induced stress causes osteopenia of the lumbar vertebrae and long bones in mice

Shimizu

Khan

Kato

et al. 2018

Sci Rep

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Excessive exposure to glucocorticoids causes osteoporosis in children and adults. Occlusal disharmony is known to induce an increase in serum corticosteroid levels in murine models, but the influence of occlusal disharmony-induced stress on the bone mass during the growth period has not yet been clarified. The purpose of this study was to investigate whether occlusal disharmony-induced stress decreases bone mass. Five-week-old C57BL/6J male mice were used. A 0.5-mm increase in the vertical height of occlusion was used to induce occlusal disharmony for a period of 7 days. Serum corticosterone levels were significantly higher on post-induction day 7, with radiological evidence of osteopenia of the third lumbar vertebra and long bones of the hind limbs. Osteopenia was associated with a reduction of the mechanical properties of the tibia and femur, with significant suppression of bone formation parameters and an increase in bone resorption parameters, as evaluated by bone histomorphometric analysis of the tibial/femur metaphysis. Our findings at the level of bones were supported by our assessment of serum markers of systemic metabolism. Therefore, occlusal disharmony-induced stress may lead to osteopenia and reduce the mechanical strength of bone through an increase in serum glucocorticoid levels in mice.Occlusal disharmony frequently occurs during growth due to mixed dentition, as the primary dentition is changing to permanent dentition. Several lines of evidence indicate that occlusal disharmony increases serum corticosteroid levels in young animals. As the serum corticosteroid level is considered to be a marker of 'stress' in rodents, it is plausible that occlusal disharmony would cause stress 1-4 . The high frequency of bruxism (teeth grinding) during the period of growth further suggests the possible existence of occlusal disharmony-induced stress in childhood [5][6][7] . By contrast, it is well known that excessive exposure to glucocorticoids causes osteopenia 8 . As an example, the use of steroid medications in children for the treatment of immune-related diseases, such as asthma and skin allergies, commonly results in bone-related side effects, including fractures and slowed bone growth 9 . Given the significant effects of stress-induced hormone on bone metabolism 10 , evaluation of the effect of occlusal disharmony-induced stress on skeletal tissue is warranted.Our aim in this study was to use a mouse model of occlusal disharmony to evaluate the effects of occlusal disharmony-induced stress on bone mass and bone mineral density, as well as on the mechanical properties of the long bones and lumbar vertebrae, which are expected to be differentially affected by mechanical loading [11][12][13] . ResultsIncrease in serum corticosterone level with occlusal disharmony. Serum corticosterone levels were measured at baseline and after the induction of occlusal disharmony (Fig. 1). Serum corticosterone levels were significantly higher in the disharmony than in the control group on post-induction days 1, 3 and 7 (Fig. ...

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Chronic Restraint Stress Upregulates Erythropoiesis through Glucocorticoid Stimulation

Cited by 29 publications

References 53 publications

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia

Low arginine vasopressin levels in patients with diabetes insipidus are not associated with anaemia

Pharmacologic activation of cholinergic alpha7 nicotinic receptors mitigates depressive-like behavior in a mouse model of chronic stress

Occlusal disharmony-induced stress causes osteopenia of the lumbar vertebrae and long bones in mice

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