title: Endogenous glucocorticoids improve myelination via Schwann cells after peripheral nerve injury: An in vivo study using a crush injury model.
abstract: Glucocorticoids improve the symptoms of peripheral nerve disorders, such as carpal tunnel syndrome and peripheral neuropathy. The effects of glucocorticoids are mainly anti-inflammatory, but the mechanisms of their effects in peripheral nerve disorders remain unclear. Schwann cells of the peripheral nerves express glucocorticoid receptors (GR), and glucocorticoids enhance the rate of myelin formation in vitro. Therefore, it is possible that the clinical improvement of peripheral nerve disorders by glucocorticoids is due, at least in part, to the modulation of myelination. In this study, an adrenalectomy (ADX) was performed, and followed by a daily injection of either low dose (1 mg/kg) or high dose (10 mg/kg) corticosterone (CORT). We then simulated a crush injury of the sciatic nerves. A sham ADX operation, followed by a simulated crush injury, was conducted as a control. Immunohistochemistry showed that the nuclei of in vivo Schwann cells expressed GR and that glucocorticoids impacted the GR immunoreactivity of the Schwann cells. The mRNA and protein expression of myelin basic protein was significantly lower in the animals given ADX with vehicle than in the sham operation group. However, the expression was restored in the low-dose CORT replacement group. Morphological analyses showed that the ADX with vehicle group had a significantly lower myelin thickness than did the low-dose CORT replacement group and the sham operation group. These results suggest that endogenous glucocorticoids have an important role in myelination through the GR in Schwann cells after an in vivo peripheral nerve injury.
authors.affiliation: Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan. mkawata@koto.kpu-m.ac.jp
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Morisaki
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nishi
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Ryo
authors.initials: R
authors.lastname: Oda
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawata
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Kubo
mesh_terms: D000315:Adrenalectomy; D000704:Analysis of Variance; D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D007211:Indoles; D008297:Male; D004676:Myelin Basic Protein / Q000235:genetics / Q000378:metabolism; D018993:Myelin P0 Protein / Q000235:genetics / Q000378:metabolism; D009409:Nerve Crush / Q000379:methods; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000502:physiology*; D020426:Sciatic Neuropathy / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D007211:Indoles; D004676:Myelin Basic Protein; D018993:Myelin P0 Protein; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D009418:S100 Proteins; C007293:DAPI; D003345:Corticosterone