Photoperiodic regulation of cellular retinoic acid-binding protein 1, GPR50 and nestin in tanycytes of the third ventricle ependymal layer of the Siberian hamster

Barrett, Perry; Ivanova, Elena; Graham, Scott E.; Ross, Alexander; Wilson, David; Plé, Hélène; Mercer, Julian G.; Ebling, Francis J. P.; Schuhler, Sandrine; Dupré, Sandrine M.; Loudon, A. S. I.; Morgan, Peter J.

doi:10.1677/joe.1.06929

Cited by 100 publications

(98 citation statements)

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“…Interestingly, in Siberian hamsters, Gpr50 expression in the ependyma of the third ventricle is downregulated in SP (1,13) and so is likely another precondition for daily torpor. We have previously demonstrated for several genes that photoperiod appropriate gene expression underpinning seasonal phenotype is largely unaltered by PAS administration (8), indicating that perception of photoperiod remains unaltered at this level.…”

Section: Discussionmentioning

confidence: 99%

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Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal

Scherbarth¹,

Diedrich²,

Dumbell³

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

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Scherbarth F, Diedrich V, Dumbell RA, Schmid HA, Steinlechner S, Barrett P. Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal. Am J Physiol Regul Integr Comp Physiol 309: R668 -R674, 2015. First published July 8, 2015 doi:10.1152/ajpregu.00191.2015 show spontaneous daily torpor only after ϳ2 mo in winter-like short photoperiods (SP). Although some SP-induced hormonal changes have been demonstrated to be necessary for the occurrence of seasonal torpor, the whole set of preconditions is still unknown. Recent findings provide evidence that the hypothalamic pituitary growth axis is involved in endocrine responses to SP exposure in the photoperiodic hamsters. To examine whether suppression of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) secretion affects the incidence of daily torpor, we used two somatostatin receptor agonists, pasireotide (SOM230) and octreotide, with different affinity profiles for receptor subtypes. Pasireotide strikingly increased the torpor frequency in male hamsters compared with sham-treated controls, and torpor duration was often increased, which in some cases exceeded 12 h. In contrast, administration of octreotide reduced the body weight of SP hamsters but had only a marginal effect on torpor frequency in males and no effect in females. Together with measured concentrations of circulating IGF-1, the present results strongly suggest that reduced activity of the GH/IGF-1 axis is not critical for stimulation of torpor expression but activation of specific somatostatin receptors is critical. This putative role for certain somatostatin receptor subtypes in torpor induction provides a promising new approach to unravel the endocrine mechanisms of torpor regulation.GH/IGF-1 axis; somatostatin receptors; torpor; seasonality; pasireotide (SOM230); octreotide SPONTANEOUS DAILY TORPOR REPRESENTS one trait of the substantial acclimation to winter-like short photoperiods (SP) in Siberian hamsters (Phodopus sungorus; a.k.a. Djungarian hamster; for review, see Ref. 26). Together with a considerably reduced body weight and improved insulative properties of the white winter fur, daily torpor contributes significantly to reduce energy demands (12). Unlike fasting-induced torpor, spontaneous daily torpor is not necessarily linked to food scarcity. Instead, Siberian hamsters show this energy-saving behavior after ϳ10 wk of SP exposure despite food abundance. Interestingly, the frequency of torpor varies largely between individuals, ranging from animals that show torpor almost every day to individuals that never enter torpor (23). Thus these hamsters exhibit an individual propensity to use this state of reduced metabolism and body temperature (T b ). Despite several decades of study, the underlying metabolic and/or hormonal factors that tip the balance in support of, or against, entry into torpor at the beginning of the (diurnal) resting phase are still unknown.SP-mediated loss of body weight appears to be a prerequisite for the occurrence of torpo...

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Section: Discussionmentioning

confidence: 99%

“…To compare hypothalamic Gpr50 expression in the ependymal layer of the third ventricle, brain sections were examined by in situ hybridization carried out as described previously (1).…”

Section: Methodsmentioning

confidence: 99%

Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal

Scherbarth¹,

Diedrich²,

Dumbell³

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

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“…Previous studies on Gpr50 expression and behavior have either used males only 10,11,16,24 or have not noted the sex of the animals, 14 possibly explaining some of the differences in expression patterns reported. Moreover, by using males, only sex-specific behaviors relevant to mental illness may be missed as women are more vulnerable to stress-related psychiatric disorders, such as PTSD and major depressive disorder.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

“…13−15 GPR50 is thought to be expressed by tanycytes, a glial cell type lining ependyma of the third ventricle, in a seasonal pattern. 16 Nothing is known however about its developmental expression.…”

mentioning

confidence: 99%

Developmental Expression of Orphan G Protein-Coupled Receptor 50 in the Mouse Brain

Grünewald

Tew

Porteous

et al. 2012

ACS Chem. Neurosci.

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Mental disorders have a complex etiology resulting from interactions between multiple genetic risk factors and stressful life events. Orphan G protein-coupled receptor 50 (GPR50) has been identified as a genetic risk factor for bipolar disorder and major depression in women, and there is additional genetic and functional evidence linking GPR50 to neurite outgrowth, lipid metabolism, and adaptive thermogenesis and torpor. However, in the absence of a ligand, a specific function has not been identified. Adult GPR50 expression has previously been reported in brain regions controlling the HPA axis, but its developmental expression is unknown. In this study, we performed extensive expression analysis of GPR50 and three protein interactors using rt-PCR and immunohistochemistry in the developing and adult mouse brain. Gpr50 is expressed at embryonic day 13 (E13), peaks at E18, and is predominantly expressed by neurons. Additionally we identified novel regions of Gpr50 expression, including brain stem nuclei involved in neurotransmitter signaling: the locus coeruleus, substantia nigra, and raphe nuclei, as well as nuclei involved in metabolic homeostasis. Gpr50 colocalizes with yeast-two-hybrid interactors Nogo-A, Abca2, and Cdh8 in the hypothalamus, amygdala, cortex, and selected brain stem nuclei at E18 and in the adult. With this study, we identify a link between GPR50 and neurotransmitter signaling and strengthen a likely role in stress response and energy homeostasis. KEYWORDS: GPR50, Nogo-A, Cadherin 8, ABCA2, rt-PCR, immunohistochemistry P sychiatric disorders are a major health problem in the world today. One in four people are affected by mental disorders during their lives, according to the World Health Organization. 1 Psychiatric illness results from the interaction between genetic and environmental risk factors. There is a strong genetic component, as is clear from family, twin, and adoption studies. 2 Recently, G protein-coupled receptor 50 (GPR50) was identified as a risk gene for bipolar disorder and major depression in Scottish women. 3,4 GPR50, previously known as the melatoninrelated receptor, is the mammalian ortholog of the melatonin 1c receptor (Mel1c). 5 Despite a 45% sequence identity to melatonin receptors MT1 and MT2, it does not bind melatonin or any other ligand and therefore remains an orphan receptor without a clear function. 6,7 We have recently reported the results of a yeast two-hybrid study (Y2H), identifying interactors with the relatively large GPR50 C-terminal domain. 8 Interactors can be grouped into two functional classes by gene ontology: neural development and sterol metabolism, indicating a likely role in these mechanisms. In addition, we showed that GPR50 has a dramatic effect on the neurite outgrowth, supporting a likely role in neural development. 8 Although the list of interactors includes several interesting protein partners, we know little about where and when these proteins could interact and what function the interactions would have.Functional evidence for a lin...

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“…En effet, l'expression du récepteur MT 1 est régulée au cours du développement et subit des variations diurnes avec un taux faible de transcrits et un taux élevé de protéines la nuit, et inversement le jour [38][39][40]. Concernant GPR50, le niveau d'expression des transcrits est régulé par la photopériode [41], mais il est aussi susceptible d'être modifié par des microARN dont les séquences cibles sont localisées au niveau de l'extrémité 3' non traduite de GPR50 [42,43]. Ainsi l'expression différentielle de MT 1 et GPR50 serait un moyen de réguler la proportion d'homo-et d'hétérodimères de GPR50 au sein d'une cellule et ainsi les effets physiologiques de la mélatonine.…”

Section: Gpr50 : Un Récepteur Orphelin à 7tm De La Famille Rhodopsineunclassified

L’hétérodimérisation des récepteurs couplés aux protéines G

Levoye

Jockers

2007

Med Sci (Paris)

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Photoperiodic regulation of cellular retinoic acid-binding protein 1, GPR50 and nestin in tanycytes of the third ventricle ependymal layer of the Siberian hamster

Cited by 100 publications

References 46 publications

Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal

Somatostatin receptor activation is involved in the control of daily torpor in a seasonal mammal

Developmental Expression of Orphan G Protein-Coupled Receptor 50 in the Mouse Brain

L’hétérodimérisation des récepteurs couplés aux protéines G

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