Acute food deprivation reduces expression of diazepam-binding inhibitor, the precursor of the anorexigenic octadecaneuropeptide ODN, in mouse glial cells

Compère, Vincent; Lanfray, Damien; Castel, Hélène; Morin, Fabrice; Leprince, Jérôme; Bertrand, Denis; Vaudry, Hubert; Pelletier, Georges; Tonon, Marie‐Christine

doi:10.1677/jme-09-0176

Cited by 22 publications

(30 citation statements)

References 24 publications

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“…Although, DBI mRNA and immunoreactivity has been found both in neurons and astrocytes (Alho et al, 1985, 1989; Tonon et al, 1990; Bouyakdan et al, 2015), DBI is mainly expressed in non-neuronal cells, such as ependymocytes, tanycytes, and proteoplasmic astrocytes (Tong et al, 1991; Lanfray et al, 2013; Bouyakdan et al, 2015). Consistent with a role of glial endozepines as anorexigenic factors, food deprivation reduces the mRNA expression of DBI in ependymocytes bordering the third and lateral ventricle as well as in median eminence tanycytes and arcuate protoplasmic astrocytes (Compère et al, 2010; Lanfray et al, 2013). The impact of endozepine signaling on neuronal populations involved in food intake control has been evaluated, with a focus on the hypothalamic leptin-sensitive neurons.…”

Section: Introductionmentioning

confidence: 67%

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level

et al. 2017

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Endozepines are endogenous ligands for the benzodiazepine receptors and also target a still unidentified GPCR. The endozepine octadecaneuropeptide (ODN), an endoproteolytic processing product of the diazepam-binding inhibitor (DBI) was recently shown to be involved in food intake control as an anorexigenic factor through ODN-GPCR signaling and mobilization of the melanocortinergic signaling pathway. Within the hypothalamus, the DBI gene is mainly expressed by non-neuronal cells such as ependymocytes, tanycytes, and protoplasmic astrocytes, at levels depending on the nutritional status. Administration of ODN C-terminal octapeptide (OP) in the arcuate nucleus strongly reduces food intake. Up to now, the relevance of extrahypothalamic targets for endozepine signaling-mediated anorexia has been largely ignored. We focused our study on the dorsal vagal complex located in the caudal brainstem. This structure is strongly involved in the homeostatic control of food intake and comprises structural similarities with the hypothalamus. In particular, a circumventricular organ, the area postrema (AP) and a tanycyte-like cells forming barrier between the AP and the adjacent nucleus tractus solitarius (NTS) are present. We show here that DBI is highly expressed by ependymocytes lining the fourth ventricle, tanycytes-like cells, as well as by proteoplasmic astrocytes located in the vicinity of AP/NTS interface. ODN staining observed at the electron microscopic level reveals that ODN-expressing tanycyte-like cells and protoplasmic astrocytes are sometimes found in close apposition to neuronal elements such as dendritic profiles or axon terminals. Intracerebroventricular injection of ODN or OP in the fourth ventricle triggers c-Fos activation in the dorsal vagal complex and strongly reduces food intake. We also show that, similarly to leptin, ODN inhibits the swallowing reflex when microinjected into the swallowing pattern generator located in the NTS. In conclusion, we hypothesized that ODN expressing cells located at the AP/NTS interface could release ODN and modify excitability of NTS neurocircuitries involved in food intake control.

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Section: Introductionmentioning

confidence: 67%

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level

et al. 2017

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“…Dbi binds GABA(A) receptors with high affinity [42], [43], and it is thought that suppression of GABAergic signaling is one mechanism through which Dbi modulates retinal neurotransmission, particularly in the inner plexiform layer [40], [41], [44], which further increases following activity-dependent phosphorylation [45], which is a hallmark of diabetes-related retinal pathology [46]. Combined with previous reports of insulin-mediated regulation of Dbi expression [47], [48], the responsiveness of Dbi protein and mRNA to insulin therapy in the present study suggests that this target may be a promising candidate for treatments focused on modulating neurovascular function in the diabetic retina.…”

Section: Discussionmentioning

confidence: 89%

Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

et al. 2011

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BackgroundAs a leading cause of adult blindness, diabetic retinopathy is a prevalent and profound complication of diabetes. We have previously reported duration-dependent changes in retinal vascular permeability, apoptosis, and mRNA expression with diabetes in a rat model system. The aim of this study was to identify retinal proteomic alterations associated with functional dysregulation of the diabetic retina to better understand diabetic retinopathy pathogenesis and that could be used as surrogate endpoints in preclinical drug testing studies.Methodology/Principal FindingsA multi-modal proteomic approach of antibody (Luminex)-, electrophoresis (DIGE)-, and LC-MS (iTRAQ)-based quantitation methods was used to maximize coverage of the retinal proteome. Transcriptomic profiling through microarray analysis was included to identify additional targets and assess potential regulation of protein expression changes at the mRNA level. The proteomic approaches proved complementary, with limited overlap in proteomic coverage. Alterations in pro-inflammatory, signaling and crystallin family proteins were confirmed by orthogonal methods in multiple independent animal cohorts. In an independent experiment, insulin replacement therapy normalized the expression of some proteins (Dbi, Anxa5) while other proteins (Cp, Cryba3, Lgals3, Stat3) were only partially normalized and Fgf2 and Crybb2 expression remained elevated.Conclusions/SignificanceThese results expand the understanding of the changes in retinal protein expression occurring with diabetes and their responsiveness to normalization of blood glucose through insulin therapy. These proteins, especially those not normalized by insulin therapy, may also be useful in preclinical drug development studies.

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“…Consistent with this observation, behavioral studies have shown that intracerebroventricular (ICV) injection of ODN and its C-terminal octapeptide (OP) fragment attenuates food consumption in rodents (Garcia de mateos-Verchere et al 2001;Do Rego et al 2007;Compère et al 2010). It has been found also that the inhibitory effect of ODN on food intake is suppressed by treatment with an antagonist of the metabotropic endozepine receptor, cyclo 1-8 [DLeu 5 ]OP (cDLOP), suggesting that the anorexigenic action of ODN is mediated via a G-protein-coupled receptor-signaling pathway but not through central-type or peripheral-type benzodiazepine receptors (Do Rego et al 2007).…”

Section: Introductionmentioning

confidence: 74%

The Anorexigenic Action of the Octadecaneuropeptide (ODN) in Goldfish is Mediated Through the MC4R- and Subsequently the CRH Receptor-Signaling Pathways

et al. 2010

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Intracerebroventricular (ICV) administration of the octadecaneuropeptide (ODN), a peptide derived from diazepam-binding inhibitor, reduces food intake in goldfish as in rodents. However, the neurochemical pathways involved in the anorexigenic action of ODN have not yet been identified in goldfish. Alpha-melanocyte-stimulating hormone (alpha-MSH), corticotropin-releasing hormone (CRH), and CRH-related peptides play a major role in the control of food consumption in goldfish. In this species, the anorexigenic action of alpha-MSH is mediated via the CRH/CRH receptor neuronal system. Therefore, in the present study, we examined whether the anorexigenic effect of ODN in goldfish could be mediated through alpha-MSH and/or CRH neuronal pathways. ICV injection of ODN (10 pmol/g body weight (BW)) significantly reduced food intake, and the anorexigenic effect of ODN was suppressed by ICV preinjection of the melanocortin 4 receptor (MC4R) antagonist HS024 (40 pmol/g BW) or the CRH receptor 1/receptor 2 antagonist alpha-helical CRH((9-41)) (100 pmol/g BW). ICV injection of ODN (10 pmol/g BW) induced a significant increase of proopiomelanocortin mRNA level but had no effect on CRH mRNA level, while ICV injection of the MC4R agonist, melanotan II (100 pmol/g BW), significantly enhanced CRH mRNA expression. These results suggest that, in goldfish, the anorexigenic action of ODN is mediated by the MC4R- and subsequently through the CRH receptor-signaling pathways.

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Acute food deprivation reduces expression of diazepam-binding inhibitor, the precursor of the anorexigenic octadecaneuropeptide ODN, in mouse glial cells

Cited by 22 publications

References 24 publications

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level

Glial Endozepines Inhibit Feeding-Related Autonomic Functions by Acting at the Brainstem Level

Multi-Modal Proteomic Analysis of Retinal Protein Expression Alterations in a Rat Model of Diabetic Retinopathy

The Anorexigenic Action of the Octadecaneuropeptide (ODN) in Goldfish is Mediated Through the MC4R- and Subsequently the CRH Receptor-Signaling Pathways

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