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Pharmacol Res Perspect. 2016 Sep 27;4(5):e00248. eCollection 2016 Oct.

Fibromyalgia syndrome: metabolic and autophagic processes in intermittent cold stress mice.

Author information

1
Department of Visceral Thoracic and Vascular Surgery Philipps University of Marburg Baldingerstrasse 35043 Marburg Germany.
2
Institute of Anatomy and Cell Biology Philipps University of Marburg Robert-Koch-Strasse 8 35032 Marburg Germany.
3
Institute for Lung Research Philipps University of Marburg Baldingerstrasse 35043 Marburg Germany.
4
Institute for Anatomy I University Hospital Erlangen Krankenhausstrasse 9 91054 Erlangen Germany.
5
Department of Gastroenterology and Endocrinology Philipps University of Marburg Baldingerstrasse 35043 Marburg Germany.
6
Developmental Biology Department of Biology Philipps University of Marburg Karl-von-Frisch-Strasse 8 35043 Marburg Germany.
7
Experimental Medicine Oncology Bayer Pharma AG Berlin Germany.
8
Institute for Medical Psychology Philipps University of Marburg Karl-von-Frisch-Strasse 4 35032 Marburg Germany.

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Abstract

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 (MAP1LC3B) 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 (COQ10B) transcript was up-regulated in limb muscle of ICS mice, whereas its protein content was stable. Cytochrome C oxidase 4 (COX4I1) 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 MAP1LC3B and BECLIN 1 (BECN1) was observed. Map1lc3b protein showed an aggregated distribution in ICS mice and SqSTM1/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.

KEYWORDS:

Autophagy; fibromyalgia syndrome; intermittent cold stress; mitochondrial dysfunction

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