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- Grönholdt-Klein, Max, et al.
(författare)
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Muscle atrophy and regeneration associated with behavioural loss and recovery of function after sciatic nerve crush
- 2019
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Ingår i: Acta Physiologica. - : John Wiley & Sons. - 1748-1708 .- 1748-1716. ; 227:3
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Tidskriftsartikel (refereegranskat)abstract
- Aim To resolve timing and coordination of denervation atrophy and the re-innervation recovery process to discern correlations indicative of common programs governing these processes. Methods Female Sprague-Dawley (SD) rats had a unilateral sciatic nerve crush. Based on longitudinal behavioural observations, the triceps surae muscle was analysed at different time points post-lesion. Results Crush results in a loss of muscle function and mass (-30%) followed by a recovery to almost pre-lesion status at 30 days post-crush (dpc). There was no loss of fibres nor any significant change in the number of nuclei per fibre but a shift in fibres expressing myosins I and II that reverted back to control levels at 30 dpc. A residual was the persistence of hybrid fibres. Early on a CHNR -epsilon to -gamma switch and a re-expression of embryonic MyHC showed as signs of denervation. Foxo1, Smad3, Fbxo32 and Trim63 transcripts were upregulated but not Myostatin, InhibinA and ActivinR2B. Combined this suggests that the mechanism instigating atrophy provides a selectivity of pathway(s) activated. The myogenic differentiation factors (MDFs: Myog, Myod1 and Myf6) were upregulated early on suggesting a role also in the initial atrophy. The regulation of these transcripts returned towards baseline at 30 dpc. The examined genes showed a strong baseline covariance in transcript levels which dissolved in the response to crush driven mainly by the MDFs. At 30 dpc the naive expression pattern was re-established. Conclusion Peripheral nerve crush offers an excellent model to assess and interfere with muscle adaptions to denervation and re-innervation.
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| 2. |
- Skoglund, Elisabeth, et al.
(författare)
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Longitudinal Muscle and Myocellular Changes in Community-Dwelling Men Over Two Decades of Successful Aging : The ULSAM Cohort Revisited
- 2020
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 75:4, s. 654-663
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Tidskriftsartikel (refereegranskat)abstract
- Participants of the population-based Uppsala longitudinal study of adult men (ULSAM) cohort reaching more than 88 years of age (survivors, S) were investigated at age 70, 82, and 88-90 and compared at 70 years with non-survivors (NS) not reaching 82 years. Body composition, muscle mass and muscle histology were remarkably stable over 18 years of advanced aging in S. Analysis of genes involved in muscle remodeling showed that S had higher mRNA levels of myogenic differentiation factors (Myogenin, MyoD), embryonic myosin (eMyHC), enzymes involved in regulated breakdown of myofibrillar proteins (Smad2, Trim32, MuRF1,) and NCAM compared with healthy adult men (n = 8). S also had higher mRNA levels of eMyHC, Smad 2, MuRF1 compared with NS. At 88 years, S expressed decreased levels of Myogenin, MyoD, eMyHC, NCAM and Smad2 towards those seen in NS at 70 years. The gene expression pattern of S at 70 years was likely beneficial since they maintained muscle fiber histology and appendicular lean body mass until advanced age. The expression pattern at 88 years may indicate a diminished muscle remodeling coherent with a decline of reinnervation capacity and/or plasticity at advanced age.
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