Molekulare und morphologische Analyse der Mitochondrienfunktion in einem Mausmodel des Fibromyalgiesyndroms

Das Fibromyalgiesyndrom (FMS) stellt eine generalisierte Tendomyopathie dar und ist beim Menschen durch großflächige, vorzugsweise muskuläre und chronische Schmerzen von mindestens drei Monaten Dauer gekennzeichnet. Die Ursache und Ätiopathogenese dieser Erkrankung sind nach wie vor unbekannt und di...

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Bibliographic Details
Main Author: Özel, Lisa
Contributors: Ocker, Matthias (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2015
Online Access:PDF Full Text
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Fibromyalgia syndrome is a generalized tendomyopathy that is characterized by widespread, particularly muscular and chronic pain of at least three months duration. The cause and pathogenesis of FMS are still unknown and diagnosis is clinically determined in accordance with classification criteria. The treatment is entirely symptomatic and does not lead to recovery from this disease. The intermittent cold stress model (ICS-model) from Nishiyori et al. induces a fibromyalgia-like pain syndrome in mice. On the basis of muscular and mitochondrial changes in patients with FMS syndrome, the present study analysed the effects of intermittent cold stress on molecular and morphologic levels in C57BL/6J mice. Therefore 9 male and 9 female mice were exposed to ICS according to the protocol of the model and compared to a control group of the same number of mice. Due to metabolic changes described in patients with FMS, different parameters were examined. Blood gas analysis showed differences concerning different parameters as CO2, Na+, Glucose, Cl-, K+,Ca2+, MetHb and O2 in ICS mice . In terms of light microscopy, a reduction of glycogen content in muscle and liver tissue was shown in male ICS-mice only. LDH-activity of mitochondrial samples was higher in ICS-mice. To indicate whether ICS has an impact on mitochondrial function, the expression of COQ10B and COX4I1 analyzed. qRT- PCR analysis showed a higher expression of Coq10b transcript in female ICS-mice. Male ICS- mice showed a significant lower expression of Cox4i1transcript. Moreover, Westernblotting implied a reduction of COQ 10B and COX4I1protein. Compliant with literature, electron micrographs of muscle tissue showed clear evidence of autophagic processes that were verified on molecular level. Thereby, significant higher expressions of the autophagy-specific genes Map1lc3b and Becn1 was detected in ICS-mice by qRT-PCR analysis. On protein level, a higher expression of SqSTM1/p62 could be perceived in mice exposed to ICS. Furthermore, ICS-mice showed an aggregated distribution of MAP1LC3B- protein in immunohistochemistry, which indicates augmented incidence of autophagosomes within autophagy. The conducted work accomplishes first insights into effects of ICS on metabolism and cell function of C57BL/6J mice and indicates the relevance of autophagic processes as well as mitochondrial and metabolic variances in muscle tissue.