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CGRP Is Critical for Hot Flushes in Ovariectomized Mice
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine.
Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
Not Found:Linkoping Univ, Dept Clin and Expt Med, Linkoping, Sweden.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
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2019 (English)In: Frontiers in Pharmacology, ISSN 1663-9812, E-ISSN 1663-9812, Vol. 9, article id 1452Article in journal (Refereed) Published
Abstract [en]

Hot flushes are common and troublesome symptoms of menopause. The neuropeptide calcitonin gene-related peptide (CGRP) is increased in plasma during hot flushes but it has not been clear if CGRP is causally involved in the mechanism underpinning the flushes. Here, we examined the effect of interventions with CGRP in a mouse model of hot flushes based on flush-like temperature increases triggered by forced physical activity in ovariectomized mice. Compared to normal mice, ovariectomized mice reacted with an exaggerated, flush-like, temperature increase after physical exercise. This increase was completely blocked by the non-peptide CGRP-antagonist MK-8825 (-0.41 degrees Celsius, 95% CI: -0,83 to 0,012, p amp;lt; 0.0001) at a dose that had no obvious effects on locomotor activity (50 mg/kg). Further, the flush-like temperature increases were strongly attenuated in ovariectomized mice lacking alpha CGRP due to a genetic modification. Collectively, our findings suggest that CGRP is an important mediator of experimentally induced hot flushes and they identify CGRP antagonists as promising treatment candidates for women and possibly also men with hot flushes.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2019. Vol. 9, article id 1452
Keywords [en]
calcitonin gene-related peptide; antagonist; thermoregulation; hot flushes; mice
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:liu:diva-153958DOI: 10.3389/fphar.2018.01452ISI: 000454889500001OAI: oai:DiVA.org:liu-153958DiVA, id: diva2:1281571
Note

Funding Agencies|Lions Foundation; County Council of Ostergotland; Swedish Medical Research Council

Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-03-29

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Wilhelms, DanielDock, HuaPettersson, EmmaStojakovic, AndreaZajdel, JoannaEngblom, DavidTheodorsson, ElvarHammar, MatsSpetz Holm, Anna-Clara
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Division of Drug ResearchFaculty of Medicine and Health SciencesDepartment of Emergency MedicineDivision of Children's and Women's healthDepartment of Clinical and Experimental MedicineDivision of Cell BiologyCenter for Social and Affective NeuroscienceDivision of Microbiology and Molecular MedicineDepartment of Clinical ChemistryDepartment of Gynaecology and Obstetrics in Linköping
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