Hypoglossal MN Dendritic Degeneration in Old Rats

Age-associated muscle weakness and atrophy (sarcopenia) is prevalent in both limb and respiratory muscles. In the tongue muscles, dyscoordination and sarcopenia predisposes elderly individuals to dysphagia, dysphonia and a greater risk for aspiration pneumonias and obstructive sleep apnea. In humans and in the Fischer 344 rat model of aging, motor neuron (MN) death occurs in old age, and the selective vulnerability of fast-fatigable motor units to loss is consistent with behavioral deficits in airway defense (e.g., cough). However, in many aerodigestive behaviors, deficits in neuromotor coordination and the timing of motor unit activations may be more pertinent than frank weakness. In motor neurons, the substrate for the integration of sensory, pattern, executive and reflex activations is the dendritic arbour. Currently, it is unknown whether MN dendritic and dendritic spine degenerations occur in aging and if any changes are specific to the vulnerable larger MNs. In this study of female and male Fischer 344 rats at 6- and 24-months-old, we evaluated hypoglossal MN dendritic arbours and dendritic spines using golgi-cox impregnation and confocal imaging approaches in thick brainstem vibratome ex vivo slices (200 µm). All data were analyzed by unpaired t-tests, 2-way ANOVAs or Pearson’s correlations, where relevant. In 24-month-old rats, hypoglossal MN dendritic arbour length and surface area were reduced compared to 6-month controls. In 6-month-olds, dendritic length and surface area was dependent on somal size, with bigger MN somas having longer and larger dendritic arbours, a relationship lost in 24-month old hypoglossal MNs. Dendritic spine density was reduced in 24- compared to 6-month-old rats. Overall, our findings suggest that hypoglossal MN dendritic degenerations with aging are selective to MNs of fast-fatigable motor units. Interventions ameliorating neuromotor circuit and dendritic breakdown may preserve neuromotor function in old age. This work was supported by NIH grants: HL166204 & AG086136 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.