ヤマウチ　カヅヨ   YAMAUCHI Kadzuyo   山内　かづ代    所属   医学部 医学科    職種   評議員
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Schwann cell LRP1 regulates remak bundle ultrastructure and axonal interactions to prevent neuropathic pain.
掲載誌名	正式名：The Journal of neuroscience : the official journal of the Society for Neuroscience 略　 称：J Neurosci ISSNコード：(1529-2401)0270-6474(Linking)
掲載区分	国外
巻・号・頁	33(13),pp.5590-602
著者・共著者	Orita Sumihisa, Henry Kenneth, Mantuano Elisabetta, Yamauchi Kazuyo, De Corato Alice, Ishikawa Tetsuhiro, Feltri M Laura, Wrabetz Lawrence, Gaultier Alban, Pollack Melanie, Ellisman Mark, Takahashi Kazuhisa, Gonias Steven L, Campana W Marie
発行年月	2013/03
概要	Trophic support and myelination of axons by Schwann cells in the PNS are essential for normal nerve function. Herein, we show that deletion of the LDL receptor-related protein-1 (LRP1) gene in Schwann cells (scLRP1(-/-)) induces abnormalities in axon myelination and in ensheathment of axons by nonmyelinating Schwann cells in Remak bundles. These anatomical changes in the PNS were associated with mechanical allodynia, even in the absence of nerve injury. In response to crush injury, sciatic nerves in scLRP1(-/-) mice showed accelerated degeneration and Schwann cell death. Remyelinated axons were evident 20 d after crush injury in control mice, yet were largely absent in scLRP1(-/-) mice. In the partial nerve ligation model, scLRP1(-/-) mice demonstrated significantly increased and sustained mechanical allodynia and loss of motor function. Evidence for central sensitization in pain processing included increased p38MAPK activation and activation of microglia in the spinal cord. These studies identify LRP1 as an essential mediator of normal Schwann cell-axonal interactions and as a pivotal regulator of the Schwann cell response to PNS injury in vivo. Mice in which LRP1 is deficient in Schwann cells represent a model for studying how abnormalities in Schwann cell physiology may facilitate and sustain chronic pain.
DOI	10.1523/JNEUROSCI.3342-12.2013
PMID	23536074