The neurobiology of urocortin

Skelton, Kelly; Owens, Michael J.; Nemeroff, Charles B.

doi:10.1016/s0167-0115(00)00180-4

Cited by 140 publications

(85 citation statements)

References 62 publications

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“…The EW has originally been identified as the source of the preganglionic parasympathetic outflow to the ciliary ganglion (Edinger, 1885;Westphal, 1887) with preganglionic autonomic neurons exhibiting choline acetyltransferase (ChAT) immunoreactivity (Kozicz et al, 2011a). However, the discovery of a distinct population of neurons that do not colocalize with ChAT immunoreactivity, and produce urocortin-1, CART and nesfatin-1 (Brailoiu et al, 2007;Foo et al, 2008;Koylu et al, 1998;Kozicz et al, 1998Kozicz et al, , 2011aVaughan et al, 1995;Xu et al, 2010), neuropeptides tied to the stress response and stress-related mood disorders such as depression, has markedly extended our insight into the functional significance of this midbrain nucleus (for reviews see: Garcia-Galiano et al, 2010;Gysling et al, 2004;Kozicz, 2007;Kozicz et al, 2011b;Pan and Kastin, 2008;Rogge et al, 2008;Skelton et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

Bloem

Morava

et al. 2012

Neuropharmacology

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a b s t r a c tAn intriguing novel pathophysiological insight into mood disorders is the notion that one's metabolic status influences mood. In rodents, cocaine-and amphetamine-regulated transcript (CART) and nesfatin-1/NUCB2 have not only been implicated in metabolism, but in the pathobiology of anxiety and depressive-like behaviour, however they have not previously been investigated in depressed subjects. Both peptides are highly expressed in centrally projecting neurons in the Edinger-Westphal nucleus (EWcp) in the midbrain. The EWcp has been implicated in stress adaptation and stress-related mood disorders like major depressive disorder in a sex-specific manner. This is intriguing, given the fact that females have higher prevalence of mood disorders. Here, we hypothesized that the expression of CART and nesfatin-1 in EWcp would exhibit a sex-specific difference between depressed suicide victims vs. controls. We found that CART and nesfatin/NUCB2 colocalized in the human EWcp, and that CART mRNA content was much higher in both male (Â3.8) and female (Â5.9) drug-free suicide victims than in controls (persons who died without any diagnosed neurodegenerative or psychiatric disorder). Similarly, NUCB2 mRNA content was also higher (Â1.8) in male suicides, whereas in female suicide victims, these contents were Â2.7 lower compared to controls. These observations are the first to show changes in the dynamics of CART and nesfatin/NUCB2 expressions in the midbrain of drug-free depressed suicide victims vs. controls.This article is part of a Special Issue entitled 'Anxiety and Depression'.

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Section: Introductionmentioning

confidence: 99%

Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

Bloem

Morava

et al. 2012

Neuropharmacology

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“…In addition to the neuropeptide CRF itself, there is a family of endogenous mammalian ligands described currently that activate these receptors called the urocortins. Urocortin 1 (UCN1) has equal affinity for both receptor subtypes although urocortin 2 and 3 (UCN2 and UCN3) have higher affinity and selectivity for the CRF 2 receptor subtype (Perrin and Vale, 1999;Skelton et al, 2000). There have been many studies, detailing the role of this family of receptors and corresponding ligands in stress-related diseases including anxiety and depression, which has generated a tremendous amount of interest in the development of novel antagonists (Grigoriadis, 2005;Holsboer, 2003;Zorrilla and Koob, 2004).…”

Section: Introductionmentioning

confidence: 99%

High-Affinity CRF1 Receptor Antagonist NBI-34041: Preclinical and Clinical Data Suggest Safety and Efficacy in Attenuating Elevated Stress Response

Ising

Zimmermann

Kuenzel

et al. 2007

Neuropsychopharmacol

134

101

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There is an extensive evidence that corticotropin releasing factor (CRF) is hypersecreted in depression and anxiety, and blockade of CRF could have therapeutic benefit. We report preclinical data and the results of a clinical Phase I study with the novel nonpeptide CRF 1 antagonist NBI-34041/SB723620. Preclinical data conducted with different cell lines expressing human CRF receptors and in Wistar and Sprague-Dawley rats indicate that NBI-34041 is effective in reducing endocrine responses to pharmacological and behavioral challenge mediated by CRF 1 receptors. These specific properties and its well-documented safety profile enabled a clinical Phase I study with 24 healthy male subjects receiving NBI-34041 (10, 50, or 100 mg) or placebo for 14 days. Regulation of the hypothalamic-pituitaryadrenocortical (HPA) axis was evaluated by intravenous stimulation with 100 mg of human CRF. Psychosocial stress response was investigated with the Trier Social Stress Test (TSST). Treatment with NBI-34041 did not impair diurnal adrenocorticotropic hormone (ACTH) and cortisol secretion or CRF evoked ACTH and cortisol responses but attenuated the neuroendocrine response to psychosocial stress. These results suggest that NBI-34041 is safe and does not impair basal regulation of the HPA system but improves resistance against psychosocial stress. NBI-34041 demonstrates that inhibition of the CRF system is a promising target for drug development against depression and anxiety disorders.

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“…Urocortin 1 (Ucn1) is a 40 amino acid peptide structurally related to CRF. It was discovered in 1995 (Vaughan et al, 1995) and although its physiological signiWcance is less extensively documented than that of CRF, it seems also to be involved in various autonomic and behavioural stress adaptation processes (e.g., Kórösi et al, 2005;Kozicz et al, 2004;Skelton et al, 2000). Recently, roles of CRF and Ucn1 in the regulation of feeding have been suggested because their central administration diminishes food intake (e.g., Heinrichs and Richard, 1999;Jones et al, 1998;Momose et al, 1999;Spina et al, 1996) and counteracts neuropeptide Y (NPY)-induced feeding (Wang et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

“…These peptides comprised factors known to be involved in some way in feeding control in mammals, namely cocaine and amphetamine-regulated transcript (CART; Douglass et al, 1995;Kuhar and Dall, 1999;Vrang et al, 1999), NPY (Stanley and Leibowitz, 1985) and metenkephalin (ENK; Gosnell and Lipton, 1986). In addition to the Mg, we studied the suprachiasmatic nucleus (SC), a main centre of NPY expression in the X. laevis brain (Tuinhof et al, 1994), the ventral hypothalamic area (VH), which is homologous with the mammalian arcuate nucleus, a main hypothalamic centre involved in the regulation of food intake (Johansen et al, 2000), the Edinger-Westphal nucleus, which is the main site of Ucn1 expression in both amphibians and mammals (Bittencourt et al, 1999;Calle et al, 2005a;Kozicz et al, 1998;Skelton et al, 2000) and is involved in the stress response in mammals (Kórösi et al, 2005;Kozicz et al, 2004), and the ventromedial thalamic nucleus (VM), which served as a negative control as it is not known to play a role in the control of feeding (ten Donkelaar, 1998).…”

Section: Introductionmentioning

confidence: 99%

Effect of starvation on Fos and neuropeptide immunoreactivities in the brain and pituitary gland of Xenopus laevis

Calle

Kozicz

Linden

et al. 2006

General and Comparative Endocrinology

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In mammals complex interactions between various brain structures and neuropeptides such as corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) underlay the control of feeding by the brain. Recently, in the amphibian Xenopus laevis, CRF-and Ucn1-immunoreactivities were shown in the hypothalamic magnocellular nucleus (Mg) and evidence was obtained for their involvement in food intake. To gain a better understanding of the brain structures controlling feeding in X. laevis, the eVects of 16 weeks starvation on neurones immunoreactive (ir) to Fos and neuropeptides in various brain structures were quantiWed. In the Mg, compared to controls, starved animals showed fewer neurones immunopositive for Fos (¡55.9%), Ucn1 (¡44.0%), cocaine and amphetamine-regulated transcript (CART) (¡94.3%) and metenkephalin (ENK) (¡65.0%), whereas CRF-ir neurones were 2.1 times more numerous. These diVerences were mainly apparent in the ventral part of the Mg, followed by the medial and dorsal part of the nucleus. In the neural lobe of the pituitary gland a 22.5% lower optical density of CART-ir was observed. In the four other brain structures investigated, starvation had diVerent eVects. The dorsomedial part of the suprachiasmatic nucleus showed 5.9 times more NPY-ir cells and in the ventromedial thalamic area a lower number of NPY-ir cells (¡33.6%) was found, whereas the Edinger-Westphal nucleus contained fewer CART-ir cells (¡42.2%); no eVect of starvation was seen in the ventral hypothalamic nucleus. Our results support the hypothesis that in X. laevis, the Mg plays a pivotal role in feeding-related processes and, moreover, that starvation also has neuropeptide-and brain structure-speciWc eVects in other parts of the brain and in the pituitary gland, suggesting particular roles of these structures and their neuropeptides in physiological adaptation to starvation.

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The neurobiology of urocortin

Cited by 140 publications

References 62 publications

Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls

High-Affinity CRF1 Receptor Antagonist NBI-34041: Preclinical and Clinical Data Suggest Safety and Efficacy in Attenuating Elevated Stress Response

Effect of starvation on Fos and neuropeptide immunoreactivities in the brain and pituitary gland of Xenopus laevis

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