Open AccessFibromyalgia syndrome: metabolic and autophagic processes in intermittent cold stress mice
Author(s) -
Oezel Lisa,
Then Hanna,
Jung Anna L.,
Jabari Samir,
Bonaterra Gabriel A.,
Wissniowski Thaddeus T.,
Önel Susanne F.,
Ocker Matthias,
Thieme Kati,
Kinscherf Ralf,
Di Fazio Pietro
Publication year - 2016
Publication title -
pharmacology research and perspectives
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 27
ISSN - 2052-1707
DOI - 10.1002/prp2.248
Subject(s) - autophagy , cytochrome c oxidase , c2c12 , mitophagy , glycogen , endocrinology , medicine , mitochondrion , apoptosis , myocyte , oxidative stress , biology , chemistry , microbiology and biotechnology , biochemistry , myogenesis
Fibromyalgia is characterized by widespread musculoskeletal pain, fatigue, and depression. The aim was to analyze potential mitochondrial dysfunction or autophagy in mice after exposure to intermittent cold stress ( ICS ). Muscle and liver specimens were obtained from 36 mice. Lactate dehydrogenase ( LDH ) activity was measured. Microtubule‐associated protein light chain 3 ( MAP 1 LC 3B) and glycogen content were determined histologically; muscle ultrastructure by electron microscopy. Mitochondrial‐ and autophagy‐related markers were analyzed by RT ‐ qPCR and Western blotting. ATP level, cytotoxicity, and caspase 3 activity were measured in murine C2C12 myoblasts after ICS exposure. Coenzyme Q10B ( COQ 10B) transcript was up‐regulated in limb muscle of ICS mice, whereas its protein content was stable. Cytochrome C oxidase 4 ( COX 4I1) and LDH activity increased in limb muscle of male ICS mice. Glycogen content was lower in muscle and liver tissue of male ICS mice. Electron micrographs of ICS mice specimens showed mitochondrial damage and autophagic vesicles. A significant up‐regulation of autophagic transcripts of MAP 1 LC 3B and BECLIN 1 ( BECN 1) was observed. Map1lc3b protein showed an aggregated distribution in ICS mice and Sq STM 1/p62 (p62) protein level was stable. Furthermore, ATP level and caspase activity, detected as apoptotic marker, were significantly lowered after ICS exposure in differentiated C2C12 myoblasts. The present study shows that ICS mice are characterized by mitochondrial dysfunction, autophagic processes, and metabolic alterations. Further investigations could dissect autophagy process in the proposed model and link these mechanisms to potential therapeutic options for fibromyalgia.