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. 2021 Jul 21;19(1):315.
doi: 10.1186/s12967-021-02989-x.

Sarcopenia associates with SNAP-25 SNPs and a miRNAs profile which is modulated by structured rehabilitation treatment

Simone Agostini  1 , Roberta Mancuso  2 , Andrea Saul Costa  2 , Franca Rosa Guerini  2 , Fabio Trecate  2 , Rossella Miglioli  2 , Elisabetta Menna  3   4 , Beatrice Arosio  5   6 , Mario Clerici  2   7 ; SA. M. B. A. project
Affiliations

Sarcopenia associates with SNAP-25 SNPs and a miRNAs profile which is modulated by structured rehabilitation treatment

Simone Agostini et al. J Transl Med. .

Abstract

Background: Sarcopenia is a loss of muscle mass and strength causing disability, morbidity, and mortality in older adults, which is characterized by alterations of the neuromuscular junctions (NMJs). SNAP-25 is essential for the maintenance of NMJ integrity, and the expression of this protein was shown to be modulated by the SNAP-25 rs363050 polymorphism and by a number of miRNAs.

Methods: We analysed these parameters in a cohort of sarcopenic patients undergoing structured rehabilitation. The rs363050 genotype frequency distribution was analyzed in 177 sarcopenic patients and 181 healthy controls (HC). The concentration of seven miRNAs (miR-451a, miR-425-5p, miR155-5p, miR-421-3p, miR-495-3p, miR-744-5p and miR-93-5p), identified by mouse brain miRNome analysis to be differentially expressed in wild type compared to SNAP-25± heterozygous mice, was analyzed as well by droplet digital PCR (ddPCR) in a subgroup of severe sarcopenic patients undergoing rehabilitation.

Results: The SNAP-25 rs363050 AA genotype was significantly more common in sarcopenic patients compared to HC (pc = 0.01); miR-451a was significantly up-regulated in these patients before rehabilitation. Rehabilitation modified miRNAs expression, as miR-155-5p, miR-421-3p, miR-451a, miR-425-5p, miR-744-5p and miR-93-5p expression was significantly up-regulated (p < 0.01), whereas that of miR-495-3p was significantly down-regulated (p < 0.001) by rehabilitation. Notably, rehabilitation-associated improvement of the muscle-skeletal SPPB score was significantly associated with the reduction of miR-451a expression.

Conclusion: These results support the hypothesis of a role for SNAP-25 in sarcopenia and suggest SNAP-25-associated miRNAs as circulatory biomarkers of rehabilitative outcome for sarcopenia.

Keywords: Biomarkers; Rehabilitation; SNAP-25; Sarcopenia; miRNAs.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
miR-451a expression (copies/ng) in serum of sarcopenic patients before and after rehabilitative treatment and age-and-sex-matched healthy controls. Horizontal bars indicate medians
Fig. 2
Fig. 2
miR-421-3p expression (copies/ng) in serum of sarcopenic patients before rehabilitative treatment. Results are divided according to SNAP-25 rs363050 categorization (AA vs. AG + GG; black dots represent GG genotype). Horizontal bars indicate medians
Fig. 3
Fig. 3
a Correlation between the change (delta) of SPPB and miR-451a expression in serum of sarcopenic patients. b miR-451a expression (copies/ng) in serum of sarcopenic patients before and after rehabilitative treatment in whom rehabilitation was (delta SPPB > 0) or was not (delta SBBP ≤ 0) successful. Horizontal bars represent medians
Fig. 4
Fig. 4
Hierarchical cluster and miRNA/KEGG pathways heat map among 7 miRNAs deregulated in brain of SNAP-25 ± vs. wild type mice. The map was obtained using the Diana tools miRPath v.3 software
See this image and copyright information in PMC

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