title: Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db-/db- mouse, a type 2 diabetes model.
abstract: Diabetic peripheral neuropathy (DPN) is the most common complication in both type 1 and type 2 diabetes. Here we studied some phenotypic features of a well-established animal model of type 2 diabetes, the leptin receptor-deficient db(-)/db(-) mouse, and also the effect of long-term (6 mo) treatment with coenzyme Q10 (CoQ10), an endogenous antioxidant. Diabetic mice at 8 mo of age exhibited loss of sensation, hypoalgesia (an increase in mechanical threshold), and decreases in mechanical hyperalgesia, cold allodynia, and sciatic nerve conduction velocity. All these changes were virtually completely absent after the 6-mo, daily CoQ10 treatment in db(-)/db(-) mice when started at 7 wk of age. There was a 33% neuronal loss in the lumbar 5 dorsal root ganglia (DRGs) of the db(-)/db(-) mouse versus controls at 8 mo of age, which was significantly attenuated by CoQ10. There was no difference in neuron number in 5/6-wk-old mice between diabetic and control mice. We observed a strong down-regulation of phospholipase C (PLC) β3 in the DRGs of diabetic mice at 8 mo of age, a key molecule in pain signaling, and this effect was also blocked by the 6-mo CoQ10 treatment. Many of the phenotypic, neurochemical regulations encountered in lumbar DRGs in standard models of peripheral nerve injury were not observed in diabetic mice at 8 mo of age. These results suggest that reactive oxygen species and reduced PLCβ3 expression may contribute to the sensory deficits in the late-stage diabetic db(-)/db(-) mouse, and that early long-term administration of the antioxidant CoQ10 may represent a promising therapeutic strategy for type 2 diabetes neuropathy.
authors.affiliation: Department of Molecular Medicine and Surgery, Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden. tiejun.shi@ki.se
authors.forename: Tie-Jun Sten
authors.initials: TJ
authors.lastname: Shi
authors.forename: Ming-Dong
authors.initials: MD
authors.lastname: Zhang
authors.forename: Hugo
authors.initials: H
authors.lastname: Zeberg
authors.forename: Johanna
authors.initials: J
authors.lastname: Nilsson
authors.forename: Jacob
authors.initials: J
authors.lastname: Grünler
authors.forename: Su-Xing
authors.initials: SX
authors.lastname: Liu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xiang
authors.forename: Jonas
authors.initials: J
authors.lastname: Persson
authors.forename: Kaj J
authors.initials: KJ
authors.lastname: Fried
authors.forename: Sergiu Bogdan
authors.initials: SB
authors.lastname: Catrina
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Peter
authors.initials: P
authors.lastname: Arhem
authors.forename: Kerstin
authors.initials: K
authors.lastname: Brismar
authors.forename: Tomas G M
authors.initials: TG
authors.lastname: Hökfelt
mesh_terms: D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology; D004558:Electric Stimulation; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000473:pathology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009431:Neural Conduction / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000517:prevention & control*; D054799:Phospholipase C beta / Q000378:metabolism; D054411:Receptors, Leptin / Q000172:deficiency* / Q000235:genetics; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology; D018709:Statistics, Nonparametric; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D014451:Ubiquinone; D054799:Phospholipase C beta; C518040:Plcb3 protein, mouse; C024989:coenzyme Q10