title: Abnormal mitochondrial dynamics and impaired mitochondrial biogenesis in trigeminal ganglion neurons in a rat model of migraine.
abstract: Accumulating evidence has demonstrated a possible role of mitochondrial dysfunction in migraine pathophysiology. Migraine sufferers exhibit impaired metabolic capacity, with an increased formation of reactive oxygen species (ROS). Mitochondrial dynamics and mitochondrial biogenesis are key processes regulating mitochondrial homeostasis. The aim of this study was to explore the alterations of mitochondrial regulatory networks in a rat model of migraine induced by repeated dural stimulation with inflammatory soup (IS). Ultrastructural, protein, gene and mitochondrial DNA analysis were applied to assess mitochondrial dynamics and biogenesis in trigeminal ganglion (TG) neurons. Mitochondria in TG neurons exhibited small and fragmented morphology after repeated dural stimulation. Further investigations showed that mitochondrial fission protein dynamin-related protein 1 (Drp1) was increased while mitochondrial fusion protein Mitofusin1 (Mfn1) was reduced in TG neurons. In addition, our results also presented that mitochondrial DNA copy number in TG neurons was reduced significantly, accompanied by alterations in mRNA and protein levels of regulatory factors related to mitochondrial biogenesis including peroxisome proliferator-activated receptor-gamma coactivator-1a (PGC-1α) and its downstream regulators in TG neurons in the IS-induced migraine model. These findings suggest that the mitochondrial dynamic regulatory networks are maladjusted in TG neurons in a rat model of migraine. Regulation of mitochondrial dynamics and biogenesis signaling may indicate a new mitochondria-targeted therapeutic strategy for migraine.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Keyan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Shanquan
authors.initials: S
authors.lastname: Jin
authors.affiliation: Department of Neurology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China.
authors.forename: Chengyun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Lanyun
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Zhaochun
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, Jiangsu Province, 210029, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, China. Electronic address: qi_wan@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wan
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000235:genetics; D018628:Gene Dosage; D008297:Male; D008881:Migraine Disorders / Q000473:pathology*; D008928:Mitochondria / Q000502:physiology / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D001678:Organelle Biogenesis; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D004272:DNA, Mitochondrial
keywords: Migraine; Mitochondrial biogenesis; Mitochondrial dynamics; Trigeminal ganglion