Hypoglossal and lumbar motor neuron death in old Sprague-Dawley rats.

Striated muscle weakness and motor neuron (MN) death are associated with aging. These alterations affect both brainstem and spinal motor pools, including hypoglossal MNs innervating the tongue and lumbar MNs innervating the lower/hindlimbs. Both MNs and striated muscles exhibit type-selective motor unit vulnerability, where larger MNs (likely fast fatigable motor units) and type IIx/b muscles are vulnerable to death and atrophy, respectively. These findings have been cemented in humans to some degree and in Fischer 344 and Wistar rats. However, MN survival in old age has not been evaluated in Sprague-Dawley rats. Here, in 6- (young) and 24-month-old (old) female and male Sprague-Dawley rats, we performed stereological MN counts on hypoglossal and lumbar MNs using 16 μm Nissl-stained sections. We observed a 35% loss of hypoglossal and lumbar MNs in old age. Although mean MN somal surface areas were moderately reduced in hypoglossal and unchanged in lumbar MNs with age, frequency histogram analyses revealed a disproportionate loss of larger MN in old age hypoglossal and lumbar pools. These findings reveal reliable and robust observations of MN death in rats. This neurogenic aspect of neuromotor impairment with age may be a key driver of sarcopenia and frailty in the elderly.