| Post-natal stress-induced endocrine and metabolic alterations in mice at adulthood involve different pro-opiomelanocortin-derived peptides. | |
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MedLine Citation:
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PMID: 20727932 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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In previous investigations we added a physical stress (mild pain) to the "classical" post-natal psychological stress in male mice, and we found that this combination produced a series of dysmetabolic signs very similar to mild human type-2 diabetes. Here, for the first time we demonstrate that within this diabetes model at least two groups of signs depend on the unbalance of two different endogenous systems. Newborn male mice were daily exposed to stressful procedures for 21 days (brief mother separation plus sham injection). Other groups underwent the same procedure, and also received naloxone (Na) to block μ-δ endogenous receptors, or a phosphorothioate antisense oligonucleotide (AS) directed against pro-opiomelanocortin (POMC)-mRNA [to block adrenocorticotropin (ACTH)- and POMC-derived opioid peptides]. Adult mice which received only post-natal stress increased body weight (+7.5%), abdominal overweight (+74%), fasting glycemia (+43%), plasma corticosterone (+110%), plasma (+169%) and pituitary (+153%) ACTH levels. Conversely, hypothalamic ACTH and corticotropin-releasing hormone (CRH) were reduced (-70% and -75%, respectively). Neonatal AS administration reverted all parameters to control values. Neonatal naloxone had little or no influence on glucose, corticosterone, ACTH, CRH levels, whereas it prevented body overweight and abdominal overweight. We conclude that, within this type-2 diabetes model in male mice at least two endocrino-neurohumoral systems are damaged, one concerning the opioid system, and the other concerning HPA hormones. The use of the two drugs was of primary importance to demonstrate this statement, and to demonstrate that these two groups of signs could be defined as "separate entities" following our complex post-natal stress model. |
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Authors:
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Stefano Loizzo; Gabriele Campana; Stefano Vella; Andrea Fortuna; Gabriella Galietta; Irene Guarino; Loredana Costa; Anna Capasso; Paolo Renzi; Giovanni V Frajese; Flavia Franconi; Alberto Loizzo; Santi Spampinato |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-08-19 |
Journal Detail:
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Title: Peptides Volume: 31 ISSN: 1873-5169 ISO Abbreviation: Peptides Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008690 Medline TA: Peptides Country: United States |
Other Details:
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Languages: eng Pagination: 2123-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Roma, Italy. stefano.loizzo@iss.it |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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