Browsing by Author "Castro, Ryan W."
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- 𝛼-Motor neurons are spared from aging while their synaptic inputs degenerate in monkeys and miceMaxwell, Nicholas; Castro, Ryan W.; Sutherland, Natalia M.; Vaughan, Kelli L.; Szarowicz, Mark D.; de Cabo, Rafael; Mattison, Julie A.; Valdez, Gregorio (Wiley, 2017)Motor 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.
- Specific labeling of synaptic schwann cells reveals unique cellular and molecular featuresCastro, Ryan W.; Taetzsch, Thomas; Vaughan, Sydney K.; Godbe, Kerilyn; Chappell, John C.; Settlage, Robert E.; Valdez, Gregorio (2020-06-25)Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study of PSCs has relied on an anatomy-based approach, as the identities of cell-specific PSC molecular markers have remained elusive. This limited approach has precluded our ability to isolate and genetically manipulate PSCs in a cell specific manner. We have identified neuron-glia antigen 2 (NG2) as a unique molecular marker of S100 beta+ PSCs in skeletal muscle. NG2 is expressed in Schwann cells already associated with the NMJ, indicating that it is a marker of differentiated PSCs. Using a newly generated transgenic mouse in which PSCs are specifically labeled, we show that PSCs have a unique molecular signature that includes genes known to play critical roles in PSCs and synapses. These findings will serve as a springboard for revealing drivers of PSC differentiation and function.