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Der Einfluss von Neuregulin-1 auf die Remyelinisierung im peripheren Nervensystem

The role of neuregulin-1 in peripheral nervous system remyelination

Ruth Martha Stassart
Doctoral thesis
Date of Examination: 2013-09-10
Date of issue: 2013-09-05
Advisor: Sereda, Michael Werner Prof. Dr.
Referee: Sereda, Michael Werner Prof. Dr.
Referee: Simons, Mikael Prof. Dr.
Referee: Oppermann, Martin Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0001-BB5C-8

 

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Abstract

English

The peripheral nervous system demonstrates an exceptional plasticity after nerve injury and Schwann cells remyelinate newly regenerated axons. However, myelin sheath thickness does not reach its original thickness and axons remain hypomyelinated after injury. During peripheral nerve development, the transmembrane growth factor neuregulin-1 type III is expressed on the axonal surface and regulates Schwann cell development as well as myelin sheath thickness. After peripheral nerve injury, Wallerian degeneration is induced and Schwann cells remain without axons and, hence, axonal neuregulin-1 type III stimulation. We demonstrate that during this time period, denervated Schwann cells strongly induce the expression of the paracrine type I isoform of neuregulin-1 which is barely detectable in non-injured nerves. Mutant mice with a specific deletion of the neuregulin-1 gene in Schwann cells are fully myelinated during development, but exhibit impaired remyelination after experimental peripheral nerve injury. We suggest a model in which loss of axonal contact triggers denervated Schwann cells to transiently express neuregulin-1 as an endogeneous signal that promotes Schwann cell redifferentiation and remyelination.
Keywords: neuregulin-1; peripheral nervous system; remyelination; Schwann cell
Schlagwörter: Neuregulin-1; Peripheres Nervensystem; Remyelinisierung; Schwannzelle
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