دورية أكاديمية

Neurochemical Characterization of Brainstem Pro-Opiomelanocortin Cells.

التفاصيل البيبلوغرافية
العنوان: Neurochemical Characterization of Brainstem Pro-Opiomelanocortin Cells.
المؤلفون: Georgescu T; Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK.; Department of Pharmacology, University of Cambridge, Cambridge, UK.; Centre for Neuroendocrinology & Department of Anatomy, University of Otago, Dunedin, New Zealand., Lyons D; Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK., Doslikova B; Department of Pharmacology, University of Cambridge, Cambridge, UK., Garcia AP; Department of Pharmacology, University of Cambridge, Cambridge, UK., Marston O; Department of Pharmacology, University of Cambridge, Cambridge, UK., Burke LK; Department of Pharmacology, University of Cambridge, Cambridge, UK., Chianese R; Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK., Lam BYH; MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK., Yeo GSH; MRC Metabolic Diseases Unit, University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK., Rochford JJ; Department of Pharmacology, University of Cambridge, Cambridge, UK., Garfield AS; Department of Pharmacology, University of Cambridge, Cambridge, UK., Heisler LK; Rowett Institute, University of Aberdeen, Foresterhill, Aberdeen, UK.; Department of Pharmacology, University of Cambridge, Cambridge, UK.
المصدر: Endocrinology [Endocrinology] 2020 Apr 01; Vol. 161 (4).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: United States NLM ID: 0375040 Publication Model: Print Cited Medium: Internet ISSN: 1945-7170 (Electronic) Linking ISSN: 00137227 NLM ISO Abbreviation: Endocrinology Subsets: MEDLINE
أسماء مطبوعة: Publication: 2017- : New York : Oxford University Press
Original Publication: Los Angeles, Calif. : Association for the Study of Internal Secretions,
مواضيع طبية MeSH: Brain Stem/*metabolism , Neurons/*metabolism , Pro-Opiomelanocortin/*metabolism , Receptors, Leptin/*metabolism, Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Cholecystokinin/metabolism ; Choline O-Acetyltransferase/metabolism ; GTP-Binding Protein gamma Subunits/metabolism ; Glucagon-Like Peptide 1/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Mice ; Mice, Transgenic ; Nitric Oxide Synthase Type I/metabolism ; Nucleobindins/metabolism ; Promoter Regions, Genetic ; Receptors, Leptin/genetics ; Tyrosine 3-Monooxygenase/metabolism
مستخلص: Genetic research has revealed pro-opiomelanocortin (POMC) to be a fundamental regulator of energy balance and body weight in mammals. Within the brain, POMC is primarily expressed in the arcuate nucleus of the hypothalamus (ARC), while a smaller population exists in the brainstem nucleus of the solitary tract (POMCNTS). We performed a neurochemical characterization of this understudied population of POMC cells using transgenic mice expressing green fluorescent protein (eGFP) under the control of a POMC promoter/enhancer (PomceGFP). Expression of endogenous Pomc mRNA in the nucleus of the solitary tract (NTS) PomceGFP cells was confirmed using fluorescence-activating cell sorting (FACS) followed by quantitative PCR. In situ hybridization histochemistry of endogenous Pomc mRNA and immunohistochemical analysis of eGFP revealed that POMC is primarily localized within the caudal NTS. Neurochemical analysis indicated that POMCNTS is not co-expressed with tyrosine hydroxylase (TH), glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), brain-derived neurotrophic factor (BDNF), nesfatin, nitric oxide synthase 1 (nNOS), seipin, or choline acetyltransferase (ChAT) cells, whereas 100% of POMCNTS is co-expressed with transcription factor paired-like homeobox2b (Phox2b). We observed that 20% of POMCNTS cells express receptors for adipocyte hormone leptin (LepRbs) using a PomceGFP:LepRbCre:tdTOM double-reporter line. Elevations in endogenous or exogenous leptin levels increased the in vivo activity (c-FOS) of a small subset of POMCNTS cells. Using ex vivo slice electrophysiology, we observed that this effect of leptin on POMCNTS cell activity is postsynaptic. These findings reveal that a subset of POMCNTS cells are responsive to both changes in energy status and the adipocyte hormone leptin, findings of relevance to the neurobiology of obesity.
(© Endocrine Society 2020.)
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معلومات مُعتمدة: WT098012 United Kingdom WT_ Wellcome Trust; BB/K001418/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; 100574/Z/12/Z United Kingdom WT_ Wellcome Trust; MRC_MC_UU_12012/5 United Kingdom MRC_ Medical Research Council; MC_UU_00014/5 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; MC_UU_12012/5 United Kingdom MRC_ Medical Research Council; BB/NO17838/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council; 093566/Z/10/A United Kingdom WT_ Wellcome Trust; MC/PC/15077 United Kingdom MRC_ Medical Research Council; 204815/Z/16/Z United Kingdom WT_ Wellcome Trust; WT081713 United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: NTS; Pomc; leptin receptor; obesity
المشرفين على المادة: 0 (Brain-Derived Neurotrophic Factor)
0 (Bscl2 protein, mouse)
0 (GTP-Binding Protein gamma Subunits)
0 (NUCB2 protein, human)
0 (Nucleobindins)
0 (Receptors, Leptin)
147336-22-9 (Green Fluorescent Proteins)
66796-54-1 (Pro-Opiomelanocortin)
89750-14-1 (Glucagon-Like Peptide 1)
9011-97-6 (Cholecystokinin)
EC 1.14.13.39 (Nitric Oxide Synthase Type I)
EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
EC 2.3.1.6 (Choline O-Acetyltransferase)
تواريخ الأحداث: Date Created: 20200314 Date Completed: 20200731 Latest Revision: 20240425
رمز التحديث: 20240425
مُعرف محوري في PubMed: PMC7102873
DOI: 10.1210/endocr/bqaa032
PMID: 32166324
قاعدة البيانات: MEDLINE
الوصف
تدمد:1945-7170
DOI:10.1210/endocr/bqaa032