Stress‐induced changes in gene expression of urocortin 2 and other <scp>CRH</scp> peptides in rat adrenal medulla: involvement of glucocorticoids

Tillinger, Andrej; Nostramo, Regina; Květňanský, Richard; Serova, Lidia; Sabban, Esther L.

doi:10.1111/jnc.12152

Cited by 15 publications

(22 citation statements)

References 53 publications

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“…Animals The immobilization (IMO) stress was conducted by gently restraining the animal in a prone position and taping its four limbs to metal mounts attached to a wooden board. This procedure was originally described by Kvetnansky and Mikulaj (1970), and it has been used in several labs (Nostramo et al, 2012;Nostramo et al, 2013;Ondrejcakova et al, 2010;Tillinger et al, 2013). In our group, the procedure has been adapted to minimize the movement of the animal and therefore the probability to induce inflammation in the paws.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

Fuentes

Carrasco

Armario

et al. 2014

Hormones and Behavior

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Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitaryadrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors.

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Section: Accepted M Manuscriptmentioning

confidence: 99%

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

Fuentes

Carrasco

Armario

et al. 2014

Hormones and Behavior

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“…It remains to be determined whether GCs induce CRH release in these neurons as they do in CRH neurons of the hypothalamus (Sorrells et al, ). However, our finding that DEX‐induced hemichannel activity in mast cells, microglia, astrocytes and oligodendrocytes as well as the response was blocked by antalarmin, which is a CRHR blocker (Stevens et al, ; Wang et al, ; Alysandratos et al, ; Tillinger et al, ), indicates DEX‐induced release of CRH. Moreover, the DEX‐induced response was mimicked by exogenous CRHR ligand, Ucn II, and its effect was also inhibited by antalamin (Fig.…”

Section: Discussionmentioning

confidence: 74%

“…Since an increase in hemichannel activity has been shown to be required for mast cell degranulation (Harcha et al, ), it is conceivable to propose that mast cells released diverse proinflammatory molecules contained in their granules (Theoharides et al, ), which 10 min later induced the hemichannel activity in microglia, astrocytes and oligodendrocytes. However, microglia and macroglia also express CRHR (Stevens et al, ; Wang et al, ; Alysandratos et al, ; Tillinger et al, ) and thus an alternative explanation could be that these cell types presented a delayed response to CRH.…”

Section: Discussionmentioning

confidence: 99%

“…CRH secreted by the hypothalamus is a key modulator of ACTH release in the HPA axis (Evanson and Herman, 2015), and is critically involved in neuroinflammatory responses to stress (Balseiro-Gomez et al, 2015). The biological actions of CRH and Ucn II (urocortin II, a member of the CRH peptide family) are mediated by CRH receptor 1 (CRHR1) and CRHR2, which are expressed in mast cells, microglia, astrocytes, and neurons (Stevens et al, 2003;Wang et al, 2007;Alysandratos et al, 2012;Tillinger et al, 2013). These receptors are involved in the increase of proinflammatory cytokine production (Stevens et al, 2003) and mediate rapid mast cell degranulation induced by CRH (Theoharides et al, 1995;Balseiro-Gomez et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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High glucocorticoid levels during gestation activate the inflammasome in hippocampal oligodendrocytes of the offspring

Maturana

Aguirre

Sáez

2016

Developmental Neurobiology

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Exposure to high levels of glucocorticoids (GCs) during early life induces long-lasting neuroinflammation. GCs induce rapid degranulation of mast cells, which release proinflammatory molecules promoting activation of microglia and astrocytes. The possible involvement of oligodendrocytes, however, remains poorly understood. It was studied whether high GC levels during gestation activates the inflammasome in hippocampal oligodendrocytes of mouse offspring. Oligodendrocytes of control pups showed expression of inflammasome components (NLRP3, ACS, and caspase-1) and their levels were increased by prenatal administration of dexamethasone (DEX), a synthetic GC. These cells also showed high levels of IL-1β and TNF-α, revealing activation of the inflammasome. Moreover, they showed increased levels of the P2X receptor and pannexin1, which are associated to inflammasome activation. However, levels of connexins either were not affected (Cx29) or reduced (Cx32 and Cx47). Nonetheless, the functional states of pannexin1 and connexin hemichannels were elevated and directly associated to functional P2X receptors. As observed in DEX-treated brain slices, hemichannel activity first increased in hippocampal mast cells and later in microglia and macroglia. DEX-induced oligodendrocyte hemichannel activity was mimicked by urocortin-II, which is a corticotropin-releasing hormone receptor (CRHR) agonist. Response to DEX and urocortin-II was inhibited by antalarmin (a CRHR blocker) or by mast cells or microglia inhibitors. The increase in hemichannel activity persisted for several weeks after birth and cross-fostering with a control mother did not reverse this condition. It is proposed that activation of the oligodendrocyte inflammasome might be relevant in demyelinating diseases associated with early life exposure to high GC levels. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 625-642, 2017.

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“…From an evolutionary perspective, UCNII belongs to one of the oldest peptide lineages conserved between species and regulates stress responses in endocrine, autonomic and immune systems (49, 50). Beside UCNIII, UCNII is the unique member of the CRH family that possesses structural features that are present in the single CRH-like peptide of tunicates and in the insect diuretic peptide (51).…”

Section: Discussionmentioning

confidence: 99%

Protective Role of the Neuropeptide Urocortin II against Experimental Sepsis and Leishmaniasis by Direct Killing of Pathogens

Campos‐Salinas

Caro

Cavazzuti

et al. 2013

The Journal of Immunology

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We currently face an alarming resurgence in infectious diseases characterized by antimicrobial resistance and therapeutic failure. This has generated the urgent need of developing new therapeutic approaches that include agents with non-traditional modes of action. A recent interest focused on approaches based on our natural immune defenses, especially on peptides which combine innate antimicrobial activity against diverse pathogens and immunoregulatory functions. Here, we describe for the first time the antimicrobial activity of the neuropeptide urocortin II (UCNII) against a panel of Gram-positive and Gram-negative bacteria and tropical parasites of the genus Leishmania. Importantly, this cytotoxicity was selective for pathogens, because UCNII did not affect mammalian cell viability. Structurally, UCNII has a cationic and amphipathic design that resembles antimicrobial peptides. Using mutants and UCNII-fragments, we determined the structural requirements for the interaction between the peptide and the surface of pathogen. Following its binding to pathogen, UCNII caused cell death through different membrane disrupting mechanisms that involve aggregation and membrane depolarization in bacteria and pore formation in Leishmania. Noteworthy, UCNII killed the infective form of L. major even inside the infected macrophages. Consequently, UCNII prevented mortality caused by polymicrobial sepsis and ameliorated pathological signs of cutaneous leishmaniasis. Besides its presence in body physical and mucosal barriers, we found that innate immune cells produce UCNII in response to infections. Therefore, UCNII could be considered as an ancient highly-conserved host peptide involved in the natural antimicrobial defense and emerge as an attractive alternative to current treatments for microbial disorders with associated drug-resistances.

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Stress‐induced changes in gene expression of urocortin 2 and other CRH peptides in rat adrenal medulla: involvement of glucocorticoids

Cited by 15 publications

References 53 publications

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats

High glucocorticoid levels during gestation activate the inflammasome in hippocampal oligodendrocytes of the offspring

Protective Role of the Neuropeptide Urocortin II against Experimental Sepsis and Leishmaniasis by Direct Killing of Pathogens

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