Abstract
SummaryMotor function deteriorates with advancing age, increasing the risk of adverse health outcomes. While it is well established that skeletal muscles and neuromuscular junctions (NMJs) degenerate with increasing age, the effect of aging on α‐motor neurons and their innervating synaptic inputs remains largely unknown. In this study, we examined the soma of α‐motor neurons and innervating synaptic inputs in the spinal cord of aged rhesus monkeys and mice, two species with vastly different lifespans. We found that, in both species, α‐motor neurons retain their soma size despite an accumulation of large amounts of cellular waste or lipofuscin. Interestingly, the lipofuscin profile varied considerably, indicating that α‐motor neurons age at different rates. Although the rate of aging varies, α‐motor neurons do not atrophy in old age. In fact, there is no difference in the number of motor axons populating ventral roots in old mice compared to adult mice. Moreover, the transcripts and proteins associated with α‐motor neurons do not decrease in the spinal cord of old mice. However, in aged rhesus monkeys and mice, there were fewer cholinergic and glutamatergic synaptic inputs directly abutting α‐motor neurons, evidence that aging causes α‐motor neurons to shed synaptic inputs. Thus, the loss of synaptic inputs may contribute to age‐related dysfunction of α‐motor neurons. These findings broaden our understanding of the degeneration of the somatic motor system that precipitates motor dysfunction with advancing age.
Highlights
We identified a-motor neurons based on: (i) their location in the ventral horn of the spinal cord, (ii) the large size of a-motor neurons compared to other neurons in the spinal cord, and (iii) the presence of vesicular acetylcholine transporter (VAChT) puncta, cholinergic inputs called Cboutons, throughout the perimeter of the soma and along the apical dendrite of a-motor neurons
Using qPCR, we found mRNA levels for HB9, Isl-1, choline acetyltransferase (ChAT), and VAChT unchanged in the spinal cord of 27-month-old mice compared to 4month-old mice (Figure S2a)
The total number of vesicular glutamate transporter 1 (VGLUT1)-positive inputs throughout the ventral horn, is unchanged in the lumbar, thoracic, and cervical regions of the spinal cord of aged mice (Figure 6d, and Figure S6b,d). These findings show that aging contributes to degeneration of glutamatergic synaptic inputs directly terminating on a-motor neurons in mice
Summary
We first examined the morphology of a-motor neurons in the spinal cord of rhesus monkeys and mice. The number of VGLUT1-positive inputs directly terminating on the somata of a-motor neurons decreased with advancing age in the lumbar, thoracic, and cervical regions of the spinal cord (Figure 6a–c and Figure S6a,c). The total number of VGLUT1-positive inputs throughout the ventral horn, is unchanged in the lumbar, thoracic, and cervical regions of the spinal cord of aged mice (Figure 6d, and Figure S6b,d). These findings show that aging contributes to degeneration of glutamatergic synaptic inputs directly terminating on a-motor neurons in mice. Providing support to this theory, published findings have shown that aging and diseases increase the accumulation of synaptic markers throughout the axoplasm in mice (Valdez, Tapia, Lichtman, Fox & Sanes, 2012)
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