Preprint SARS-CoV-2 induces acute neurological signs while CGRP signaling blockade reduces IL-6 release and weight loss in mouse models, 2023, Rahman et al.

SARS-CoV-2 induces acute neurological signs while Calcitonin Gene-Related Peptide CGRP signaling blockade reduces interleukin 6 IL-6 release and weight loss in mouse models
Shafaqat M Rahman; David W Buchholz; Brian Imbiakha; Mason C Jaeger; Justin Leach; Raven M Osborn; Ann O Birmingham; Stephen Dewhurst; Hector C Aguilar; Anne E Luebke

COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection.

We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 αCGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking αCGRP.

These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.


Link | PDF (Preprint: BioRxiv)