scholarly journals Coordinated action of CRH and cortisol shapes acute stress-induced behavioural response in zebrafish

2021 ◽  
Author(s):  
Erin Faught ◽  
Mathilakath M. Vijayan

Introduction: The stress response mediated by the hypothalamus-pituitary-adrenal (HPA) axis activation is highly conserved in vertebrates. Hyperactivity is one such established acute stress response and corticotropin-releasing hormone (CRH), the primary step in HPA activation, signalling has been implicated in this stressor-mediated behaviour. However, whether CRH mediates the acute behavioural effects either alone or in conjunction with glucocorticoids (GCs) are far from clear. We hypothesized that the CRH receptor 1 (CRHR1)-mediated rise in GCs post-stress is necessary for the initiation and maintenance of acute stress-related behaviour. Methods: We first generated zebrafish (Danio rerio) with a mutation in the crhr1 gene (CRHR1-KO) to assess the function of CRH. The behavioural readout utilized for this study was the locomotor activity of larval zebrafish in response to acute light exposure, a protocol that freezes the larvae in response to the light stimulus. To test whether cortisol signalling is involved in the stress-mediated hyperactivity, we treated wildtype fish with metyrapone, an inhibitor of 11β-hydroxylase, to suppress cortisol production. The temporal role for cortisol signalling in the stress-related hyperactivity was tested using the glucocorticoid receptor (GRKO) and mineralocorticoid receptor (MRKO) knockout zebrafish mutants. Results: CRHR1-KO larvae did not increase cortisol, the principal GC in teleosts, post-stress, confirming a functional knockout. An acute stress resulted in the hyperactivity of the larvae in light at 15, 60 and 240 min post-stress and this was absent in CRHR1-KO larvae. Addition of metyrapone effectively blocked the attendant rise in cortisol post-stress; however, the stress-mediated hyperactivity was inhibited only at 60 min and 240 min but not at 15 min post-stress. Addition of human CRH peptide caused hyperactivity at 15 min and this response was also abolished in the CRHR1-KO mutants. The stress-induced hyperactivity was absent in the MRKO fish, while GRKO mutants showed transient effects. Conclusions: The results suggest that the stress-induced hyperactivity is induced by the CRH/CRHR1 system, while the temporal activation of cortisol production and the associated GR/MR signalling is essential for prolonging the stressor-induced hyperactivity. This study underscores the importance of systems-level analysis to assess stress responsivity.

2020 ◽  
Vol 86 (1) ◽  
pp. 39-45
Author(s):  
H. Kozhyna ◽  
O.V. Druz ◽  
K. Zelenska ◽  
I. Chernenko

The clinical phenomenology of post-stress disorders was studied in combatants. We observed 150 servicemen of the Armed Forces of Ukraine, who took a direct part in the fighting in the ATO zone, in accordance with the principles of bioethics and deontology on the basis of the National Military Medical Clinical Center «Main Military Clinical Hospital» and the Military Medical Center of the Northern Region. It is shown, that the clinical structure of post-stress disorders in combatants is represented by posttraumatic stress disorder (PTSD), acute stress response and adjustment disorders. The clinical structure of PTSD in combatants is represented by anxious (35.2 % of men and 44.2 % of women), dysphoric (33.5 % and 9.4 %), asthenic (25.4 % and 32.6 %) and somatoform (5.9 % and 13.8 %) syndrome complexes. Adjustment disorders included prolonged depressive reaction (10.1 % of men and 15.7 % of women), mixed anxiety-depressive reaction (16.5 % and 10.2 %), adjustment disorders with a predominance of disturbances of other emotions (9.8 % and 7.4 %). The major risk factors for the development of stress-related disorders in combatants were identified: prolonged participation in combat, the need to see and touch the bodies of the dead, the threat of death from sniper’s fire, the death of friends in their own eyes, the impact of harmful combat factors, family conflicts, adverse social and economic circumstances. The correlation analysis was carried out. It was found, that the severity of psychopathological symptoms is determined by the severity of combat mental trauma. High scores on the Mississippi scale are associated with prolonged mental trauma (rxy=0.64), threat of death (rxy=0.58), death of comrades (rxy=0.54), participation in close combat (rxy=0.50), the offensive (rxy=0.41), the need to touch the bodies of the dead (rxy=0.46), with the killing of opponents (rxy=0.45). There is a strong correlation of combat mental trauma with anxiety intensity (rxy=0.78), fear (rxy=0.71), sense of internal tension (rxy=0.70), disturbance of the sleep-wake cycle (rxy=0.70), incontinence of affect (rxy=0.69) and depression (rxy=0.66). Keywords: post-traumatic stress disorder, adjustment disorders, acute stress response, combat mental trauma, correlation analysis.


2013 ◽  
Vol 46 (06) ◽  
Author(s):  
I Elbau ◽  
SA Kiem ◽  
A Prosser ◽  
I Eidner ◽  
M Czisch ◽  
...  

Author(s):  
Alexander S. Häusl ◽  
Lea M. Brix ◽  
Jakob Hartmann ◽  
Max L. Pöhlmann ◽  
Juan-Pablo Lopez ◽  
...  

AbstractDisturbed activation or regulation of the stress response through the hypothalamic-pituitary-adrenal (HPA) axis is a fundamental component of multiple stress-related diseases, including psychiatric, metabolic, and immune disorders. The FK506 binding protein 51 (FKBP5) is a negative regulator of the glucocorticoid receptor (GR), the main driver of HPA axis regulation, and FKBP5 polymorphisms have been repeatedly linked to stress-related disorders in humans. However, the specific role of Fkbp5 in the paraventricular nucleus of the hypothalamus (PVN) in shaping HPA axis (re)activity remains to be elucidated. We here demonstrate that the deletion of Fkbp5 in Sim1+ neurons dampens the acute stress response and increases GR sensitivity. In contrast, Fkbp5 overexpression in the PVN results in a chronic HPA axis over-activation, and a PVN-specific rescue of Fkbp5 expression in full Fkbp5 KO mice normalizes the HPA axis phenotype. Single-cell RNA sequencing revealed the cell-type-specific expression pattern of Fkbp5 in the PVN and showed that Fkbp5 expression is specifically upregulated in Crh+ neurons after stress. Finally, Crh-specific Fkbp5 overexpression alters Crh neuron activity, but only partially recapitulates the PVN-specific Fkbp5 overexpression phenotype. Together, the data establish the central and cell-type-specific importance of Fkbp5 in the PVN in shaping HPA axis regulation and the acute stress response.


2011 ◽  
Vol 132 (3) ◽  
pp. 103-109 ◽  
Author(s):  
Toshimitsu Komatsu ◽  
Lucas S. Trindade ◽  
Takuya Chiba ◽  
Hiroko Hayashi ◽  
Tomoko Henmi ◽  
...  

2003 ◽  
Vol 285 (5) ◽  
pp. R1098-R1106 ◽  
Author(s):  
Rogier D. van Anholt ◽  
Tom Spanings ◽  
William Koven ◽  
Sjoerd E. Wendelaar Bonga

The cyclooxygenase (COX) pathway converts arachidonic acid (ArA) into prostaglandins (PGs), which interact with the stress response in mammals and possibly in fish as well. Acetylsalicylic acid (ASA) is a COX inhibitor and was used to characterize the effects of PGs on the release of several hormones and the stress response of tilapia ( Oreochromis mossambicus). Plasma PGE2 was significantly reduced at 100 mg ASA/kg body wt, and both basal PGE2 and cortisol levels correlated negatively with plasma salicylate. Basal plasma 3,5,3′-triiodothyronine (T3) was reduced by ASA treatment, whereas prolactin (PRL)188 increased at 100 mg ASA/kg body wt. ASA depressed the cortisol response to the mild stress of 5 min of net confinement. As expected, glucose and lactate were elevated in the stressed control fish, but the responses were blunted by ASA treatment. Gill Na+-K+-ATPase activity was not affected by ASA. Plasma osmolarity increased after confinement in all treatments, whereas sodium only increased at the high ASA dose. This is the first time ASA has been administered to fish in vivo, and the altered hormone release and the inhibition of the acute stress response indicated the involvement of PGs in these processes.


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