Loss of calcitonin gene-related peptide (αCGRP) and use of a vestibular challenge highlight balance deficiencies in aging mice

Abstract

Aging impacts the vestibular system and contributes to imbalance. In fact, imbalance precedes changes in cognition in the elderly. However, research is limited in assessing aging mouse models that are deficient in crucial 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. Postural sway and rotarod testing were performed before and after a vestibular challenge (VC) in the 129S wild type and the αCGRP (-/-) null mice. Four age groups were tested that correspond to young adulthood, late adulthood, middle age, and senescence in humans. Our results suggest wild type mice experience a decline in rotarod ability due to aging after they reach their prime performance at 6–10 months of age, while the αCGRP (-/-) null mice perform poorly on rotarod early in life but improve with age as they get older, potentially due to vestibular compensation. 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 αCGRP (-/-) null but requires future studies to evaluate anxiety effects. These results indicate that αCGRP is an important component of proper balance and that the loss of αCGRP can contribute to balance complications that may compound with aging.