Age-Related Balance Problems in Mice Are Sharpened by the Loss of Calcitonin Gene-Related Peptide (CGRP) and a Vestibular Challenge

Abstract

Aging impacts the vestibular system and contributes to imbalance. In fact, in the elderly balance deficits often precede changes in cognition. However, imbalance research is limited in assessing aging mouse models that are deficient in neuromodulators like Calcitonin Gene-Related Peptide (CGRP). We studied the loss of CGRP and its effects in the aging mouse, namely its effect on both static and dynamic imbalances. In addition, postural sway and rotarod testing were performed before and after a vestibular challenge (VC) in the 129S wildtype and the CGRP (-/-) null mice. Four age groups were tested that correspond to young adulthood, late adulthood, middle age, and senescence in humans. Our results suggest wildtype mice experience a decline in rotarod ability with increased age, while the CGRP (-/-) null mice perform poorly on rotarod early in life and do not improve. Our postural sway study suggests that a vestibular challenge can lead to significantly reduced CoP ellipse areas (freezing behaviors) in older mice, and this change occurs earlier in the CGRP (-/-) null mouse. These results indicate that CGRP is an important component of static and dynamic balance; and that the loss of CGRP can contribute to balance complications that may compound with aging.