A cortical neuropeptide with neuronal depressant and sleep-modulating properties

Lecea, Luı́s de; Criado, José R.; Prospéro-Garcı́a, Oscar; Gautvik, Kaare M.; Schweitzer, Paul; Danielson, Patria E.; Dunlop, Charles L. M.; Siggins, George R.; Henriksen, Steven J.; Sutcliffe, J. Gregor

doi:10.1038/381242a0

Cited by 388 publications

(294 citation statements)

References 19 publications

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“…Control experiments included the omission of the primary antibody in serial sections or, in the case of CST IHC, pre-absorption of the primary antibody with a 100-fold excess of CST-17 (Phoenix Pharmaceutical) or of SRIF-14 (Bachem Feinchemikalien, AG Bubendorf, Switzerland). Cerebral cortex or pancreatic islets [2,14] and human testis [12] served as positive controls for CST and MrgX2, respectively.…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

“…Cortistatin (CST) is a 17-amino acid neuropeptide recently discovered in rat, mouse, and humans that exhibits strong structural homology to somatostatin (SRIF) [1][2][3][4]. The human CST gene was mapped to chromosome 1p36.3-p36.2 and found to contain two exons separated by a 1 kb intron [3,5].…”

Section: Introductionmentioning

confidence: 99%

“…Two mature products, CST-17 and CST-29, are generated by a prohormone convertase, the former being equivalent to murine CST-14, a cyclic peptide that shares 11 of its 14 amino acid residues with SRIF-14, responsible for SRIF binding to its receptors [1,2].…”

Section: Introductionmentioning

confidence: 99%

“…CST-17 and CST-29 bind to all five SRIF receptors (subtypes [1][2][3][4][5] with an affinity comparable to that of SRIF-14 [6]. In addition, both CST-14 and CST-17, but not SRIF-14, are also able to bind the ghrelin receptor type 1a (growth hormone secretagogue receptor -GHS-R1a) [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

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Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours

et al. 2005

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Cortistatin (CST), a novel hormone originally described in the rat, mouse, and human cerebral cortex, displays structural and functional similarities to somatostatin (SRIF). CST binds to all five somatostatin receptors and, differently from SRIF, also binds to MrgX2, which has recently been identified as its specific receptor. Little is known about the distribution of CST and MrgX2 in peripheral non-tumour and neoplastic tissues. The aim of the present study was therefore to determine by immunohistochemistry and mRNA analysis (RT-PCR) the distribution of CST and MrgX2 in 56 human non-tumour and 108 tumour tissues, with special reference to neuroendocrine tissue types. Despite the high level of CST mRNA expression in non-tumour and tumour (both neuroendocrine and nonneuroendocrine) tissues, the presence of immunoreactive CST was confirmed in a subset of gastroenteropancreatic, parathyroid, and pituitary non-tumour cells only, and showed a predominantly focal pattern in most neuroendocrine tumours. Co-localization experiments in the gastroenteropancreatic system demonstrated that the normal CST-producing cells are δ cells, while in the adenohypophysis no preferential co-localization of CST with any of the pituitary hormones was observed. MrgX2 mRNA was variably detected in the hypothalamus, pituitary, thyroid, lung, gastroenteropancreatic tract, testis, and ovary, and was negative in the cerebral cortex, parathyroid, and adrenal, as well as in a variety of tumour types. Conversely, immunolocalization of MrgX2 protein was restricted to neurohypophysis and testis, whilst all tumours analysed were negative. A possible explanation for the discrepancy between RT-PCR and immunohistochemistry is that MrgX2 protein was widely detected in blood vessels, scattered lymphocytes, and gastrointestinal ganglia in both normal and neoplastic samples. The findings demonstrate a selective distribution of CST in normal and neoplastic neuroendocrine tissues, suggesting that CST might have a broader functional role than previously assumed, whereas possible autocrine/paracrine actions via its recently described specific receptor MrgX2 are restricted to selected tissues.

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Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours

et al. 2005

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“…La pertinence de cette approche comparative avait déjà été validée avec la découverte de la sécrétoneurine [7], de la cortistatine [8] et de l'urotensine II [9] chez l'homme, trois neuropeptides initialement isolés à partir du cerveau de la grenouille [10][11][12]. Afin de rechercher de nouveaux membres de la famille des peptides RFamide chez les vertébrés, les chercheurs rouennais ont criblé des fractions pré-purifiées d'un extrait de cerveaux de grenouille à l'aide d'un anticorps dirigé contre le motif Arg-Phe-NH 2 .…”

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Où l’on apprend comment la grenouille pourrait se faire aussi grosse que le boeuf…

2004

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Diagnostic Specificity and Association With Cognition of Molecular Alterations in Prefrontal Somatostatin Neurons in Schizophrenia

Dienel,

Dowling,

Barile

et al. 2023

JAMA Psychiatry

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ImportanceIndividuals with schizophrenia (SZ) exhibit pronounced deficits in somatostatin (SST) messenger RNA (mRNA) levels in the dorsolateral prefrontal cortex (DLPFC). Molecularly distinct subtypes of SST neurons, located in the superficial and deep zones of the DLPFC, are thought to contribute to different functional processes of this region; understanding the specificity of SST alterations in SZ across these zones could inform the functional consequences of those alterations, including cognitive impairments characteristic of SZ.ObjectiveTo quantify mRNA levels of SST and related neuropeptides in the DLPFC in individuals with SZ, bipolar disorder (BPD), or major depressive disorder (MDD) and unaffected comparison individuals.Design, Setting, and ParticipantsThis case-control study, conducted from January 20, 2020, to March 30, 2022, used postmortem brain tissue specimens previously obtained from individuals with SZ, MDD, or BPD and unaffected individuals from a community population through 2 medical examiners’ offices. Demographic, clinical, and educational information was ascertained through psychological autopsies.ExposuresDiagnosis of SZ, BPD, or MDD.Main Outcome and MeasuresThe main outcome was levels of SST and related neuropeptide mRNA in 2 DLPFC zones, examined using laser microdissection and quantitative polymerase chain reaction or fluorescent in situ hybridization (FISH). Findings were compared using educational attainment as a proxy measure of premorbid cognition.ResultsA total of 200 postmortem brain specimens were studied, including 65 from unaffected comparison individuals (42 [65%] male; mean [SD] age, 49.2 [14.1] years); 54 from individuals with SZ (37 [69%] male; mean [SD] age, 47.5 [13.3] years); 42 from individuals with MDD (24 [57%] male; mean [SD] age, 45.6 [12.1] years); and 39 from individuals with BPD (23 [59%] male; mean (SD) age, 46.2 [12.5] years). Compared with unaffected individuals, levels of SST mRNA were lower in both superficial (Cohen d, 0.68; 95% CI, 0.23-1.13; P = .004) and deep (Cohen d, 0.60; 95% CI, 0.16-1.04; P = .02) DLPFC zones in individuals with SZ; findings were confirmed using FISH. Levels of SST were lower only in the superficial zone in the group with MDD (Cohen d, 0.58; 95% CI, 0.14-1.02; P = .12), but the difference was not significant; SST levels were not lower in either zone in the BPD group. Levels of neuropeptide Y and tachykinin 1 showed similar patterns. Neuropeptide alterations in the superficial, but not deep, zone were associated with lower educational attainment only in the group with SZ (superficial: adjusted odds ratio, 1.71 [95% CI, 1.11-2.69]; P = .02; deep: adjusted odds ratio, 1.08 [95% CI, 0.64-1.84]; P = .77).Conclusions and RelevanceThe findings revealed diagnosis-specific patterns of molecular alterations in SST neurons in the DLPFC, suggesting that distinct disease processes are reflected in the differential vulnerability of SST neurons in individuals with SZ, MDD, and BPD. In SZ, alterations specifically in the superficial zone may be associated with cognitive dysfunction.

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A cortical neuropeptide with neuronal depressant and sleep-modulating properties

Cited by 388 publications

References 19 publications

Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours

Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours

Où l’on apprend comment la grenouille pourrait se faire aussi grosse que le boeuf…

Diagnostic Specificity and Association With Cognition of Molecular Alterations in Prefrontal Somatostatin Neurons in Schizophrenia

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