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Publication : CGRP Is Critical for Hot Flushes in Ovariectomized Mice.

First Author  Wilhelms DB Year  2018
Journal  Front Pharmacol Volume  9
Pages  1452 PubMed ID  30662401
Mgi Jnum  J:277633 Mgi Id  MGI:6342318
Doi  10.3389/fphar.2018.01452 Citation  Wilhelms DB, et al. (2018) CGRP Is Critical for Hot Flushes in Ovariectomized Mice. Front Pharmacol 9:1452
abstractText  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 < 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 alphaCGRP 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.
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