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A mutation in desmin makes skeletal muscle less vulnerable to acute muscle damage after eccentric loading in rats.

ABSTRACT: Desminopathy is the most common intermediate filament disease in humans. The most frequent mutation causing desminopathy in patients is a R350P DES missense mutation. We have developed a rat model with an analogous mutation in R349P Des. To investigate the role of R349P Des in mechanical loading, we stimulated the sciatic nerve of wild-type littermates (WT) (n = 6) and animals carrying the mutation (MUT) (n = 6) causing a lengthening contraction of the dorsi flexor muscles. MUT animals showed signs of ongoing regeneration at baseline as indicated by a higher number of central nuclei (genotype: P < .0001). While stimulation did not impact central nuclei, we found an increased number of IgG positive fibers (membrane damage indicator) after eccentric contractions with both genotypes (stimulation: P < .01). Interestingly, WT animals displayed a more pronounced increase in IgG positive fibers with stimulation compared to MUT (interaction: P < .05). In addition to altered histology, molecular signaling on the protein level differed between WT and MUT. The membrane repair protein dysferlin decreased with eccentric loading in WT but increased in MUT (interaction: P < .05). The autophagic substrate p62 was increased in both genotypes with loading (stimulation: P < .05) but tended to be more elevated in WT (interaction: P = .05). Caspase 3 levels, a central regulator of apoptotic cell death, was increased with stimulation in both genotypes (stimulation: P < .01) but more so in WT animals (interaction: P < .0001). Overall, our data indicate that R349P Des rats have a lower susceptibility to structural muscle damage of the cytoskeleton and sarcolemma with acute eccentric loading.

SUBMITTER: Langer HT

PROVIDER: S-EPMC9292853 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: We set out to investigate the effectiveness of grounded sleeping on the time course of recovery with respect to muscle soreness and athletic performance after intensive eccentric muscle loading. Methods: Twenty-two healthy participants were recruited for this study and randomly assigned to an experimental group (GRD, grounded sleeping, n = 12) or control group (UGD, sham-grounded sleeping, n = 10) to evaluate the effects of 10 days recovery with GRD vs. UGD following a single intensive downhill treadmill intervention in a triple-blinded (participant, tester, and data analyst) manner. To operationalize recovery a test battery was performed at baseline and on days 1, 2, 3, 5, 7, and 10 post-intervention: (1) perception of muscle soreness (VAS), (2) creatine kinase blood levels (CK), (3) maximum voluntary isometric contraction (MVIC) for both legs, (4) counter movement jump (CMJ) and drop jump (DJ) performance. Furthermore, in four participants blood was sampled for detailed analysis of complete blood counts and serum-derived inflammation markers. Results: The downhill treadmill running intervention led to distinct changes in all measured parameters related to fatigue. These changes were detectable already 5-min post intervention and were not fully recovered 10 days post intervention. GRD led to less pronounced decrease in performance (CMJ, MVIC) and less increase with respect to CK compared with UGD (all P < 0.05). Detailed blood samples demonstrated that grounded sleeping modulates the recovery process by (a) keeping a constant hemoconcentration, as represented by the number of erythrocytes, and the hemoglobin/hematocrit values; and (b) by the reduction of muscle damage-associated inflammation markers such as, IP-10, MIP-1?, and sP-Selectin. Conclusion: The downhill running protocol is a feasible methodology to produce long term muscle soreness and muscular fatigue. GRD was shown to result in faster recovery and/or less pronounced markers of muscle damage and inflammation. GRD might be seen as a simple methodology to enhance acute and long-term recovery after intensive eccentric exercises.

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A mutation in desmin makes skeletal muscle less vulnerable to acute muscle damage after eccentric loading in rats.

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