线粒体生物发生
TFAM公司
神经炎症
MFN2型
MFN1型
第一季
线粒体
内分泌学
生物
医学
内科学
线粒体融合
药理学
化学
细胞生物学
线粒体DNA
炎症
生物化学
基因
作者
Ylenia Marino,Francesca Inferrera,Ramona D’Amico,Daniela Impellizzeri,Marika Cordaro,Rosalba Siracusa,Enrico Gugliandolo,Roberta Fusco,Salvatore Cuzzocrea,Rosanna Di Paola
标识
DOI:10.1016/j.bbadis.2024.167301
摘要
A critical role for mitochondrial dysfunction has been shown in the pathogenesis of fibromyalgia. It is a chronic pain syndrome characterized by neuroinflammation and impaired oxidative balance in the central nervous system. Boswellia serrata (BS), a natural polyphenol, is a well-known able to influence the mitochondrial metabolism. The objective of this study was to evaluate the mitochondrial dysfunction and biogenesis in fibromyalgia and their modulation by BS. To induce the model reserpine (1 mg/Kg) was subcutaneously administered for three consecutive days and BS (100 mg/Kg) was given orally for twenty-one days. BS reduced pain like behaviors in reserpine-injected rats and the astrocytes activation in the dorsal horn of the spinal cord and prefrontal cortex that are recognized as key regions associated with the neuropathic pain. Vulnerability to neuroinflammation and impaired neuronal plasticity have been described as consequences of mitochondrial dysfunction. BS administration increased PGC-1α expression in the nucleus of spinal cord and brain tissues, promoting the expression of regulatory genes for mitochondrial biogenesis (NRF-1, Tfam and UCP2) and cellular antioxidant defence mechanisms (catalase, SOD2 and Prdx 3). According with these data BS reduced lipid peroxidation and the GSSG/GSH ratio and increased SOD activity in the same tissues. Our results also showed that BS administration mitigates cytochrome-c leakage by promoting mitochondrial function and supported the movement of PGC-1α protein into the nucleus restoring the quality control of mitochondria. Additionally, BS reduced Drp1 and Fis1, preventing both mitochondrial fission and cell death, and increased the expression of Mfn2 protein, facilitating mitochondrial fusion. Overall, our results showed important mitochondrial dysfunction in central nervous system in fibromyalgia syndrome and the role of BS in restoring mitochondrial dynamics.
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