Myelin-associated glycoprotein in myelin and expressed by Schwann cells inhibits axonal regeneration and branching

被引:109
作者
Shen, YJ
DeBellard, ME
Salzer, JL
Roder, J
Filbin, MT
机构
[1] CUNY Hunter Coll, Dept Biol Sci, New York, NY 10021 USA
[2] NYU, Med Ctr, Dept Cell Biol & Neurol, Sch Med, New York, NY 10016 USA
[3] Mt Sinai Hosp, Toronto, ON M5GG 1X5, Canada
关键词
D O I
10.1006/mcne.1998.0700
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The mammalian CNS does not regenerate after injury due largely to myelin-specific inhibitors of axonal growth. The PNS, however, does regenerate once myelin is cleared and myelin proteins are down-regulated by Schwann cells. Myelin-associated glycoprotein (MAG), a sialic acid binding protein, is a potent inhibitor of neurite outgrowth when presented to neurons in culture. Here, we present additional evidence that strongly supports the suggestion that MAG contributes to the overall inhibitory properties of myelin. When myelin from MAG-/- mice is used as a substrate, axonal length is 100 and 60% longer for neonatal cerebellar and older DRG neurons, respectively, compared to MAG+/+ myelin. The converse is true for neurites from neonatal DRG neurons, which are twice as long on MAG+/+ relative to MAG-/- myelin, consistent with MAG's dual role of promoting axonal growth from neonatal DRG neurons but inhibiting growth in older DRG and all other postnatal neurons examined. Furthermore, desialylating neurons reverses inhibition by CNS myelin by 45%. Contrary to previous reports, under these conditions PNS myelin is also inhibitory for axonal regeneration. Importantly, results using PNS MAG-/- myelin as a substrate suggest that MAG contributes to this inhibition. Finally, when Schwann cells not expressing MAG and permissive for axonal growth are induced to express MAG by retroviral infection, not only is axonal outgrowth greatly inhibited by these cells but so also is neurite branching. This suggests for the first time that MAG not only affects axonal regeneration but may also play a role in the control of axonal sprouting.
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页码:79 / 91
页数:13
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