Hypocortisolism and impaired stress responses in Bmal1-deficient mice

2013 ◽  
Vol 121 (10) ◽  
Author(s):  
A Leliavski ◽  
A Shostak ◽  
J Husse ◽  
H Oster
Keyword(s):  
Stress Responses ◽  
Deficient Mice

scholarly journals Plasma Transcortin Influences Endocrine and Behavioral Stress Responses in Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 649-659 ◽  
Author(s):  
Elodie M. Richard ◽  
Jean-Christophe Helbling ◽  
Claudine Tridon ◽  
Aline Desmedt ◽  
Amandine M. Minni ◽  
...  
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Learned Helplessness ◽  
Critical Role ◽  
Adaptive Responses ◽  
Adrenal Axis ◽  
Response To Stress ◽  
Hypothalamus Pituitary Adrenal Axis ◽  
Deficient Mice ◽  
Pituitary Adrenal Axis

Glucocorticoids are released after hypothalamus-pituitary-adrenal axis stimulation by stress and act both in the periphery and in the brain to bring about adaptive responses that are essential for life. Dysregulation of the stress response can precipitate psychiatric diseases, in particular depression. Recent genetic studies have suggested that the glucocorticoid carrier transcortin, also called corticosteroid-binding globulin (CBG), may have an important role in stress response. We have investigated the effect of partial or total transcortin deficiency using transcortin knockout mice on hypothalamus-pituitary-adrenal axis functioning and regulation as well as on behaviors linked to anxiety and depression traits in animals. We show that CBG deficiency in mice results in markedly reduced total circulating corticosterone at rest and in response to stress. Interestingly, free corticosterone concentrations are normal at rest but present a reduced surge after stress in transcortin-deficient mice. No differences were detected between transcortin-deficient mice for anxiety-related traits. However, transcortin-deficient mice display increased immobility in the forced-swimming test and markedly enhanced learned helplessness after prolonged uncontrollable stress. The latter is associated with an approximately 30% decrease in circulating levels of free corticosterone as well as reduced Egr-1 mRNA expression in hippocampus in CBG-deficient mice. Additionally, transcortin-deficient mice show no sensitization to cocaine-induced locomotor responses, a well described corticosterone-dependent test. Thus, transcortin deficiency leads to insufficient glucocorticoid signaling and altered behavioral responses after stress. These findings uncover the critical role of plasma transcortin in providing an adequate endocrine and behavioral response to stress.

scholarly journals Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader–Willi syndrome

2020 ◽  
Author(s):  
Rui-Ni Wu ◽  
Wei-Chen Hung ◽  
Ching-Tsuey Chen ◽  
Li-Ping Tsai ◽  
Wen-Sung Lai ◽  
...  
Keyword(s):  
Animal Model ◽  
Locus Coeruleus ◽  
Neuronal Activity ◽  
Stress Responses ◽  
Neurodevelopmental Disorder ◽  
Pain Modulation ◽  
Prader Willi Syndrome ◽  
Firing Activity ◽  
Diverse Range ◽  
Deficient Mice

Abstract Background Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. Methods Heterozygous necdin-deficient mice (B6.Cg-Ndn tm1ky ) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/−p) animals, which were examined of LC-NE neuronal activity, developmental reflexes and plethysmography. Results On slice electrophysiology, LC-NE neurons of Ndn tm1ky mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndn tm1ky mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. Conclusions LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.

scholarly journals Hepatocyte-Specific Phgdh-Deficient Mice Culminate in Mild Obesity, Insulin Resistance, and Enhanced Vulnerability to Protein Starvation

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3468
Author(s):  
Momoko Hamano ◽  
Kayoko Esaki ◽  
Kazuki Moriyasu ◽  
Tokio Yasuda ◽  
Sinya Mohri ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stress Responses ◽  
De Novo ◽  
Molecular Signatures ◽  
Significant Gain ◽  
Phosphoglycerate Dehydrogenase ◽  
Protein Free Diet ◽  
Protein Starvation ◽  
Mild Obesity ◽  
Deficient Mice

L-Serine (Ser) is synthesized de novo from 3-phosphoglycerate via the phosphorylated pathway committed by phosphoglycerate dehydrogenase (Phgdh). A previous study reported that feeding a protein-free diet increased the enzymatic activity of Phgdh in the liver and enhanced Ser synthesis in the rat liver. However, the nutritional and physiological functions of Ser synthesis in the liver remain unclear. To clarify the physiological significance of de novo Ser synthesis in the liver, we generated liver hepatocyte-specific Phgdh KO (LKO) mice using an albumin-Cre driver. The LKO mice exhibited a significant gain in body weight compared to Floxed controls at 23 weeks of age and impaired systemic glucose metabolism, which was accompanied by diminished insulin/IGF signaling. Although LKO mice had no apparent defects in steatosis, the molecular signatures of inflammation and stress responses were evident in the liver of LKO mice. Moreover, LKO mice were more vulnerable to protein starvation than the Floxed mice. These observations demonstrate that Phgdh-dependent de novo Ser synthesis in liver hepatocytes contributes to the maintenance of systemic glucose tolerance, suppression of inflammatory response, and resistance to protein starvation.

scholarly journals Urocortin-Deficient Mice Display Normal Stress-Induced Anxiety Behavior and Autonomic Control but an Impaired Acoustic Startle Response

2002 ◽  
Vol 22 (18) ◽  
pp. 6605-6610 ◽  
Author(s):  
Xiaozhong Wang ◽  
Hong Su ◽  
Leslie D. Copenhagen ◽  
Sukishi Vaishnav ◽  
Fredalina Pieri ◽  
...  
Keyword(s):  
Stress Responses ◽  
Startle Response ◽  
Acoustic Startle ◽  
Acoustic Startle Response ◽  
Embryonic Stem ◽  
Autonomic Responses ◽  
Hearing Defect ◽  
Response To Stress ◽  
Anxiety Behavior ◽  
Deficient Mice

ABSTRACT Corticotropin-releasing hormone (Crh) plays an important role in modulating physiological and behavioral responses to stress. Its actions are mediated through two receptors, Crhr1 and Crhr2. Urocortin (Ucn), a Crh-related neuropeptide and the postulated endogenous ligand for Crhr2, is a potential mediator of stress responses. We generated Ucn-deficient mice using embryonic stem cell technology to determine its role in stress-induced behavioral and autonomic responses. Unlike Crhr1- or Crhr2-deficient mice, Ucn-deficient mice exhibit normal anxiety-like behavior as well as autonomic regulation in response to stress. However, the mutant mice display an impaired acoustic startle response that is not due to an obvious hearing defect. Thus, our results suggest that Ucn does not play an essential role in stress-induced behavioral and autonomic responses. Ucn may modulate the acoustic startle response through the Ucn-expressing neuron projections from the region of the Edinger-Westphal nucleus.

scholarly journals Co-released Norepinephrine and Galanin Act on Different Timescales to Promote Stress-Induced Anxiety-Like Behavior

2020 ◽  
Author(s):  
Rachel P. Tillage ◽  
Stephanie L. Foster ◽  
Daniel Lustberg ◽  
L. Cameron Liles ◽  
David Weinshenker
Keyword(s):  
Stress Responses ◽  
Acute Stress ◽  
Noradrenergic Neurons ◽  
Wild Type ◽  
Functional Roles ◽  
Behavioral Stress ◽  
Normal Expression ◽  
Individual Contributions ◽  
The Individual ◽  
Deficient Mice

ABSTRACTBackgroundBoth the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, and these two neuromodulators are co-released from the stress-responsive locus coeruleus (LC); however, the individual contributions of LC-derived norepinephrine (NE) and galanin to behavioral stress responses are unclear. Here we aimed to disentangle the functional roles of co-released NE and galanin in stress-induced behavior.MethodsWe used foot shock, optogenetics, and behavioral pharmacology in wild-type (WT) mice and mice lacking either NE (Dbh-/-) or galanin (GalcKO-Dbh) specifically in noradrenergic neurons to isolate the roles of these co-transmitters in regulating anxiety-like behavior in the elevated zero maze (EZM) either immediately or 24 h following stress.ResultsFoot shock and optogenetic LC stimulation produced immediate anxiety-like behavior in WT mice, and the effects of foot shock persisted for 24 h. NE-deficient mice were resistant to the anxiogenic effects of acute stress and optogenetic LC stimulation, while mice lacking noradrenergic-derived galanin displayed typical increases in anxiety-like behavior. However, when tested 24 h after foot shock, both Dbh-/- and GalcKO-Dbh mice lacked normal expression of anxiety-like behavior. Pharmacological rescue of NE, but not galanin, in knockout mice during EZM testing was anxiogenic. In contrast, restoring galanin, but not NE, signaling during foot shock normalized stress-induced anxiety-like behavior 24 h later.ConclusionsThese results indicate that NE and noradrenergic-derived galanin play complementary, but distinguishable roles in behavioral responses to stress. NE is required for the expression of acute stress-induced anxiety, while noradrenergic-derived galanin mediates more persistent responses following a stressor.

scholarly journals Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader–Willi syndrome

2020 ◽  
Author(s):  
Rui-Ni Wu ◽  
Wei-Chen Hung ◽  
Ching-Tsuey Chen ◽  
Li-Ping Tsai ◽  
Wen-Sung Lai ◽  
...  
Keyword(s):  
Animal Model ◽  
Locus Coeruleus ◽  
Neuronal Activity ◽  
Stress Responses ◽  
Neurodevelopmental Disorder ◽  
Pain Modulation ◽  
Prader Willi Syndrome ◽  
Firing Activity ◽  
Diverse Range ◽  
Deficient Mice

Abstract Background Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. Methods Heterozygous necdin-deficient mice (B6.Cg-Ndn tm1ky ) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/−p) animals, which were examined of LC-NE neuronal activity, developmental reflexes and plethysmography. Results On slice electrophysiology, LC-NE neurons of Ndn tm1ky mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndn tm1ky mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. Conclusions LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.

Anxiety and Stress Responses in Female Oxytocin Deficient Mice

2004 ◽  
Vol 16 (4) ◽  
pp. 319-324 ◽  
Author(s):  
J. A. Amico ◽  
R. C. Mantella ◽  
R. R. Vollmer ◽  
X. Li
Keyword(s):  
Stress Responses ◽  
Deficient Mice

scholarly journals Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader–Willi syndrome

2020 ◽  
Author(s):  
Rui-Ni Wu ◽  
Wei-Chen Hung ◽  
Ching-Tsuey Chen ◽  
Li-Ping Tsai ◽  
Wen-Sung Lai ◽  
...  
Keyword(s):  
Animal Model ◽  
Locus Coeruleus ◽  
Neuronal Activity ◽  
Stress Responses ◽  
Neurodevelopmental Disorder ◽  
Pain Modulation ◽  
Prader Willi Syndrome ◽  
Firing Activity ◽  
Diverse Range ◽  
Deficient Mice

Abstract Background: Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS.Methods: Heterozygous necdin-deficient mice (B6.Cg-Ndntm1ky) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/−p) animals, which were examined of LC-NE neuronal activity, developmental reflexes and plethysmography.Results: On slice electrophysiology, LC-NE neurons of Ndntm1ky mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndntm1ky mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia.Conclusions: LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.

Comparison of localization of metallothionein in tissues of metallothionein-deficient mice

1995 ◽  
Vol 53 ◽  
pp. 1042-1043
Author(s):  
H. Nishimura ◽  
R Nishimura ◽  
D.L. Adelson ◽  
A.E. Michaelska ◽  
K.H.A. Choo ◽  
...  
Keyword(s):  
Metal Binding ◽  
Immunohistochemical Staining ◽  
Squamous Epithelium ◽  
Rabbit Antiserum ◽  
Slight Modification ◽  
Positive Control ◽  
Heavy Metal Binding ◽  
Critical Organ ◽  
Metal Binding Protein ◽  
Deficient Mice

Metallothionein (MT), a cysteine-rich heavy metal binding protein, has several isoforms designated from I to IV. Its major isoforms, I and II, can be induced by heavy metals like cadmium (Cd) and, are present in various organs of man and animals. Rodent testes are a critical organ to Cd and it is still a controversial matter whether MT exists in the testis although it is clear that MT is not induced by Cd in this tissue. MT-IV mRNA was found to localize within tongue squamous epithelium. Whether MT-III is present mainly glial cells or neurons has become a debatable topic. In the present study, we have utilized MT-I and II gene targeted mice and compared MT localization in various tissues from both MT-deficient mice and C57Black/6J mice (C57BL) which were used as an MT-positive control. For MT immunostaining, we have used rabbit antiserum against rat MT-I known to cross-react with mammalian MT-I and II and human MT-III. Immunohistochemical staining was conducted by the method described in the previous paper with a slight modification after the tissues were fixed in HistoChoice and embedded in paraffin.

Sign in / Sign up

Export Citation Format

Share Document