The time course of neuromuscular impairment during short-term disuse in young women.

Skeletal muscle disuse results in rapid functional declines. Previous studies have typically been at least 1 week in duration and focused on the responsiveness of men. Herein, we report the timeline of initial impairments in strength, voluntary activation (VA), and motor unit control during 2 weeks of knee joint immobilization. Thirteen women (mean age =21 years) underwent 2 weeks of left knee joint immobilization via ambulation on crutches and use of a brace. Participants visited the laboratory for testing on seven occasions (two familiarization visits, pretest, 48 and 72 h, 1 and 2 weeks). Knee extensor isometric and concentric isokinetic strength at two velocities (180 and 360 degrees⋅s-1 ), VA, and submaximal vastus lateralis motor unit activity were evaluated. Moderate-to-large decreases in isometric and concentric strength at 180 degrees⋅s-1 and VA were observed within 48 hours. Isometric strength continued to decline beyond 72 h, whereas other variables plateaued. The B-term of the motor unit mean firing rate versus action potential amplitude relationship demonstrated a moderate increase 1 week into immobilization, suggesting that greater firing rates were necessary to maintain pretest torque levels. Concentric strength at a velocity of 360 degrees s-1 was not affected. Decreases in knee extensor strength occur within a matter of days after immobilization, although the time course and magnitude vary among assessment methods. These changes are mediated by the nervous system's capacity to activate skeletal muscle. Clinically appropriate interventions which target nervous system plasticity should be implemented early to minimize the rapid functional impairments associated with disuse.

The microtubule regulator ringer functions downstream from the RNA repair/splicing pathway to promote axon regeneration.

Promoting axon regeneration in the central and peripheral nervous system is of clinical importance in neural injury and neurodegenerative diseases. Both pro- and antiregeneration factors are being identified. We previously reported that the Rtca mediated RNA repair/splicing pathway restricts axon regeneration by inhibiting the nonconventional splicing of Xbp1 mRNA under cellular stress. However, the downstream effectors remain unknown. Here, through transcriptome profiling, we show that the tubulin polymerization-promoting protein (TPPP) ringmaker/ringer is dramatically increased in Rtca-deficient Drosophila sensory neurons, which is dependent on Xbp1. Ringer is expressed in sensory neurons before and after injury, and is cell-autonomously required for axon regeneration. While loss of ringer abolishes the regeneration enhancement in Rtca mutants, its overexpression is sufficient to promote regeneration both in the peripheral and central nervous system. Ringer maintains microtubule stability/dynamics with the microtubule-associated protein futsch/MAP1B, which is also required for axon regeneration. Furthermore, ringer lies downstream from and is negatively regulated by the microtubule-associated deacetylase HDAC6, which functions as a regeneration inhibitor. Taken together, our findings suggest that ringer acts as a hub for microtubule regulators that relays cellular status information, such as cellular stress, to the integrity of microtubules in order to instruct neuroregeneration.