title: Morphological Alterations in Gastrocnemius and Soleus Muscles in Male and Female Mice in a Fibromyalgia Model.
abstract: BACKGROUND
  Fibromyalgia (FM) is a chronic musculoskeletal pain disorder, characterized by chronic widespread pain and bodily tenderness and is often accompanied by affective disturbances, however often with unknown etiology. According to recent reports, physical and psychological stress trigger FM. To develop new treatments for FM, experimental animal models for FM are needed to be development and characterized. Using a mouse model for FM including intermittent cold stress (ICS), we hypothesized that ICS leads to morphological alterations in skeletal muscles in mice.
  
  
  METHODS
  Male and female ICS mice were kept under alternating temperature (4 °C/room temperature [22 °C]); mice constantly kept at room temperature served as control. After scarification, gastrocnemius and soleus muscles were removed and snap-frozen in liquid nitrogen-cooled isopentane or fixed for electron microscopy.
  
  
  RESULTS
  In gastrocnemius/soleus muscles of male ICS mice, we found a 21.6% and 33.2% decrease of fiber cross sectional area (FCSA), which in soleus muscle concerns the loss of type IIa and IIx FCSA. This phenomenon was not seen in muscles of female ICS mice. However, this loss in male ICS mice was associated with an increase in gastrocnemius of the density of MIF+ (8.6%)-, MuRF+ (14.7%)-, Fbxo32+ (17.8%)-cells, a 12.1% loss of capillary contacts/muscle fiber as well as a 30.7% increase of damaged mitochondria in comparison with male control mice. Moreover, significant positive correlations exist among densities (n/mm(2)) of MIF+, MuRF+, Fbxo32+-cells in gastrocnemius/ soleus muscles of male ICS mice; these cell densities inversely correlate with FCSA especially in gastrocnemius muscle of male ICS mice.
  
  
  CONCLUSIONS
  The ICS-induced decrease of FCSA mainly concerns gastrocnemius muscle of male mice due to an increase of inflammatory and atrogenic cells. In soleus muscle of male ICS and soleus/gastrocnemius muscles of female ICS mice morphological alterations seem to occur not at all or delayed. The sex-specificity of findings, which is not easily reconciled with the epidemiology of FM (female predominance), implicate that gastrocnemius muscle of male ICS mice should preferentially be used for future investigations with FM. Moreover, we suggest to investigate morphological and/or molecular alterations at different time-points (up to two weeks) after ICS.
authors.affiliation: Anatomy und Cell Biology, Department of Medical Cell Biology, University of Marburg, Marburg, Hessen, Germany.
authors.forename: Gabriel Alejandro
authors.initials: GA
authors.lastname: Bonaterra
authors.affiliation: Anatomy und Cell Biology, Department of Medical Cell Biology, University of Marburg, Marburg, Hessen, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Then
authors.affiliation: Institute for Surgical Research, Philipps University of Marburg, Marburg, Hessen, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Oezel
authors.affiliation: Anatomy und Cell Biology, Department of Medical Cell Biology, University of Marburg, Marburg, Hessen, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Schwarzbach
authors.affiliation: Institute for Surgical Research, Philipps University of Marburg, Marburg, Hessen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ocker
authors.affiliation: Institute for Medical Psychology, Philipps University of Marburg, Marburg, Hessen, Germany.
authors.forename: Kati
authors.initials: K
authors.lastname: Thieme
authors.affiliation: Institute for Surgical Research, Philipps University of Marburg, Marburg, Hessen, Germany.
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Fazio
authors.affiliation: Anatomy und Cell Biology, Department of Medical Cell Biology, University of Marburg, Marburg, Hessen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kinscherf
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005356:Fibromyalgia / Q000473:pathology*; D053583:Interleukin-1beta / Q000032:analysis; D019746:Intramolecular Oxidoreductases / Q000032:analysis; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000473:pathology; D009124:Muscle Proteins / Q000032:analysis; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology*; D044843:SKP Cullin F-Box Protein Ligases / Q000032:analysis; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000032:analysis
chemical_list: D053583:Interleukin-1beta; D008263:Macrophage Migration-Inhibitory Factors; D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse