XII MN Histology Golgi-Cox Data from Christensen, T.A., Fogarty, M.J. 2026, https://doi.org/10.1007/s11357-025-02075-w

Hypoglossal motor neurons (MNs) within the medullary hypoglossal nucleus innervate the striated muscles of the intrinsic and extrinsic tongue. Dysfunction of the control of the tongue muscles may lead to problems such as dysphagia, dysphonia and the increased risk of aspiration pneumonia in the elderly. In the human and Fischer 344 (F344) rat motor systems, age-related muscle weakness and behavioural dysfunctions are contemporaneous to MN death. In other neurons, dendritic and mitochondrial degenerations are fundamental pathophysiological components preceding neuronal death. We aimed to determine if dendritic, dendritic spine and dendritic mitochondrial pathology were present in old age. We used golgi-cox and serial block-face scanning electron microscopy (SBFSEM) to evaluate dendritic and mitochondrial morphology, respectively in young (6-month) and old (24-month) female and male F344 rats. Dendritic regression and dendritic spine loss occurs in old age, predominantly in larger hypoglossal MNs. In addition, reduced dendritic mitochondrial volume density and mitochondrial fragmentation are apparent in old age. Our results are consistent with established age-related deficits in F344 rats, including tongue muscle sarcopenia, hypoglossal MN loss and dysphagia. Although more work is needed to determine if synaptic and mitochondrial degenerations are causative for age-related neuromotor dysfunctions, our results suggest that strategies to preserve dendrites and mitochondria may be of therapeutic utility.