Anxiolytic- and antidepressant-like actions of Urocortin 2 and its fragments in mice

Bagosi, Zsolt; Csabafi, Krisztina; Balangó, Beáta; Pintér, Dávid; Szolomájer-Csikós, Orsolya; Bozsó, Zsolt; Tóth, Gábor; Telegdy, Gyula; Szabó, Gyula

doi:10.1016/j.brainres.2017.12.011

Cited by 4 publications

(3 citation statements)

References 37 publications

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“…The FS test is generally used to determine depressive behavior in animal models of psychiatric disorders [20,21]. Here, we used the FS test to determine behavioral abnormalities in pups because high cortisol level is critically correlated with depressive behavioral patterns in adult rodents [9,10].…”

Section: Cortipups Exhibit Hyperactive Behavior In Fs Testmentioning

confidence: 99%

Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats

Jeon

Kim

et al. 2021

Exp Neurobiol

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High levels of cortisol in blood are frequently observed in patients with major depressive disorders and increased cortisol level induces depressivelike symptoms in animal models. However, it is still unclear whether maternal cortisol level during pregnancy is a critical factor resulting in neuropsychiatric disorders in offspring. In this study, we increased cortisol level in rats by repetitively injecting corticosterone subcutaneously (Corti. Mom, 20 mg/kg/day) during pregnancy and evaluated the behavioral patterns of their pups (Corti.Pups) via forced swimming (FS), open field (OF), elevated plus maze (EPM) and Morris water maze (MWM) tests during the immediate post-weaning period (postnatal day 21 to 25). In results, corticosterone significantly increased plasma cortisol levels in both Corti.Moms and Corti.Pups. Unlike depressive animal models, Corti.Pups showed higher hyperactive behaviors in the FS and OF tests than normal pups (Nor.Pups) born from rats (Nor.Moms) treated with saline. Furthermore, Corti.Pups spent more time and traveled longer distance in the open arms of EPM test, exhibiting higher extremity. These patterns were consistent with behavioral symptoms observed in animal models of attention deficit hyperactivity disorder (ADHD), which is characterized by hyperactivity, impulsivity, and inattention. Additionally, Corti.Pups swam longer and farther to escape in MWM test, showing cognitive declines associated with attention deficit. Our findings provide evidence that maternal cortisol level during pregnancy may affect the neuroendocrine regulation and the brain development of offspring, resulting in heterogeneous developmental brain disorders such as ADHD.

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Section: Cortipups Exhibit Hyperactive Behavior In Fs Testmentioning

confidence: 99%

Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats

Jeon

Kim

et al. 2021

Exp Neurobiol

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“…Although exogenous administration of Ucn 2 has been reported to have anxiolytic effects in the EPM test, the range of anxiolytic effects of Ucn2 is very narrow ( 49 ). Ucn 2-deficient mice have been reported to show no alteration in open % in the EPM test ( 55 ).…”

Section: Discussionmentioning

confidence: 99%

“…Actions of Ucn 2 such as anorexigenic effect and the increase of motor activity are exhibited through the binding to CRF type 2 receptors, which are distributed in various area of the brainlateral septal nucleus, bed nucleus, medial nucleus of the amygdala, ventromedial nucleus of the hypothalamus, dorsal raphe, and subcortical structures (46)(47)(48). A previous study demonstrated that the central administration of Ucn 2 in mice had an antidepressant effect as demonstrated in the FS test (49). Furthermore, Ucn 2 has been shown to ameliorate depression-like behavior induced in nicotine-withdrawal model mice via the CRF type 2 receptor (50).…”

Section: Discussionmentioning

confidence: 99%

Musclin prevents depression-like behavior in male mice by activating urocortin 2 signaling in the hypothalamus

Ataka,

Asakawa,

Iwai

et al. 2023

Front. Endocrinol.

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IntroductionPhysical activity is recommended as an alternative treatment for depression. Myokines, which are secreted from skeletal muscles during physical activity, play an important role in the skeletal muscle-brain axis. Musclin, a newly discovered myokine, exerts physical endurance, however, the effects of musclin on emotional behaviors, such as depression, have not been evaluated. This study aimed to access the anti-depressive effect of musclin and clarify the connection between depression-like behavior and hypothalamic neuropeptides in mice.MethodsWe measured the immobility time in the forced swim (FS) test, the time spent in open arm in the elevated-plus maze (EPM) test, the mRNA levels of hypothalamic neuropeptides, and enumerated the c-Fos-positive cells in the paraventricular nucleus (PVN), arcuate nucleus (ARC), and nucleus tractus solitarii (NTS) in mice with the intraperitoneal (i.p.) administration of musclin. Next, we evaluated the effects of a selective corticotropin-releasing factor (CRF) type 1 receptor antagonist, selective CRF type 2 receptor antagonist, melanocortin receptor (MCR) agonist, and selective melanocortin 4 receptor (MC4R) agonist on changes in behaviors induced by musclin. Finally we evaluated the antidepressant effect of musclin using mice exposed to repeated water immersion (WI) stress.ResultsWe found that the i.p. and i.c.v. administration of musclin decreased the immobility time and relative time in the open arms (open %) in mice and increased urocortin 2 (Ucn 2) levels but decreased proopiomelanocortin levels in the hypothalamus. The numbers of c-Fos-positive cells were increased in the PVN and NTS but decreased in the ARC of mice with i.p. administration of musclin. The c-Fos-positive cells in the PVN were also found to be Ucn 2-positive. The antidepressant and anxiogenic effects of musclin were blocked by central administration of a CRF type 2 receptor antagonist and a melanocortin 4 receptor agonist, respectively. Peripheral administration of musclin also prevented depression-like behavior and the decrease in levels of hypothalamic Ucn 2 induced by repeated WI stress.DiscussionThese data identify the antidepressant effects of musclin through the activation of central Ucn 2 signaling and suggest that musclin and Ucn 2 can be new therapeutic targets and endogenous peptides mediating the muscle−brain axis.

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Melanin-concentrating hormone in the Locus Coeruleus aggravates helpless behavior in stressed rats

Urbanavicius

Fabius

Roncalho

et al. 2019

Behavioural Brain Research

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Anxiolytic- and antidepressant-like actions of Urocortin 2 and its fragments in mice

Cited by 4 publications

References 37 publications

Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats

Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats

Musclin prevents depression-like behavior in male mice by activating urocortin 2 signaling in the hypothalamus

Melanin-concentrating hormone in the Locus Coeruleus aggravates helpless behavior in stressed rats

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