Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice

Peter Hjørringgaard Larsen, Angelika G. DaSilva, Kathrine Conant, V. Wee Young

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: februar 2006
OriginalsprogEngelsk
TidsskriftJournal of Neuroscience
Vol/bind26
Udgave nummer8
Sider (fra-til)2207-2214
Antal sider7
ISSN0270-6474
StatusUdgivet - 1. feb. 2006

Fingeraftryk

Matrix Metalloproteinase 12
Matrix Metalloproteinase 9
Myelin Sheath
Matrix Metalloproteinases
Oligodendroglia
Insulin-Like Growth Factor Binding Protein 6
Corpus Callosum
Optic Nerve
Nervous System

Bibliografisk note

Paper id:: PMID: 16495447 [PubMed - indexed for MEDLINE]

Citer dette

Larsen, P. H., DaSilva, A. G., Conant, K., & Young, V. W. (2006). Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice. Journal of Neuroscience, 26(8), 2207-2214.
Larsen, Peter Hjørringgaard ; DaSilva, Angelika G. ; Conant, Kathrine ; Young, V. Wee. / Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice. I: Journal of Neuroscience. 2006 ; Bind 26, Nr. 8. s. 2207-2214.
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title = "Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice",
abstract = "The matrix metalloproteinases (MMPs) are implicated in several activities within the nervous system. Although many functions of abnormally elevated MMPs are undesirable, the discrete expression of particular MMP members can have beneficial roles. We previously found that MMP-9 expressed locally around a demyelinating lesion of the spinal cord of adult mice facilitated remyelination. In the current study, we have addressed whether and how MMPs might be required for myelin formation in normal ontogeny. Using a probe for multiple MMPs and the developing mouse optic nerve, we found two members, MMP-9 and -12, to be upregulated during the period of myelin formation. These MMPs partake in myelinogenesis because myelination in the corpus callosum of MMP-9 and/or MMP-12 null mice was deficient from postnatal days 7 to 14 compared with that of wild-type mice. The deficient myelination was correlated with fewer mature oligodendrocytes, but similar precursor cell numbers, in MMP null animals compared with wild type. Because an important growth factor for oligodendrocyte maturation is insulin-like growth factor-1 (IGF-1), we addressed whether this was involved in the deficient myelination in MMP null mice. Indeed, the addition of IGF-1 normalized the lack of maturation of oligodendrocytes that occurred in cultures from MMP-12 null mice. Furthermore, we determined that IGF binding protein 6 (IGFBP-6), which sequesters IGF-1, was a substrate for MMP processing. Finally, we found IGFBP-6 levels to remain high in MMP-deficient mice. These results reveal a novel function for MMP-9 and -12 in developmental myelination likely through regulating IGF-1 bioavailability.",
author = "Larsen, {Peter Hj{\o}rringgaard} and DaSilva, {Angelika G.} and Kathrine Conant and Young, {V. Wee}",
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Larsen, PH, DaSilva, AG, Conant, K & Young, VW 2006, 'Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice', Journal of Neuroscience, bind 26, nr. 8, s. 2207-2214.

Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice. / Larsen, Peter Hjørringgaard; DaSilva, Angelika G.; Conant, Kathrine; Young, V. Wee.

I: Journal of Neuroscience, Bind 26, Nr. 8, 01.02.2006, s. 2207-2214.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Myelin Formation during Development of the CNS Is Delayed in Matrix Metalloproteinase-9 and -12 Null Mice

AU - Larsen, Peter Hjørringgaard

AU - DaSilva, Angelika G.

AU - Conant, Kathrine

AU - Young, V. Wee

N1 - Paper id:: PMID: 16495447 [PubMed - indexed for MEDLINE]

PY - 2006/2/1

Y1 - 2006/2/1

N2 - The matrix metalloproteinases (MMPs) are implicated in several activities within the nervous system. Although many functions of abnormally elevated MMPs are undesirable, the discrete expression of particular MMP members can have beneficial roles. We previously found that MMP-9 expressed locally around a demyelinating lesion of the spinal cord of adult mice facilitated remyelination. In the current study, we have addressed whether and how MMPs might be required for myelin formation in normal ontogeny. Using a probe for multiple MMPs and the developing mouse optic nerve, we found two members, MMP-9 and -12, to be upregulated during the period of myelin formation. These MMPs partake in myelinogenesis because myelination in the corpus callosum of MMP-9 and/or MMP-12 null mice was deficient from postnatal days 7 to 14 compared with that of wild-type mice. The deficient myelination was correlated with fewer mature oligodendrocytes, but similar precursor cell numbers, in MMP null animals compared with wild type. Because an important growth factor for oligodendrocyte maturation is insulin-like growth factor-1 (IGF-1), we addressed whether this was involved in the deficient myelination in MMP null mice. Indeed, the addition of IGF-1 normalized the lack of maturation of oligodendrocytes that occurred in cultures from MMP-12 null mice. Furthermore, we determined that IGF binding protein 6 (IGFBP-6), which sequesters IGF-1, was a substrate for MMP processing. Finally, we found IGFBP-6 levels to remain high in MMP-deficient mice. These results reveal a novel function for MMP-9 and -12 in developmental myelination likely through regulating IGF-1 bioavailability.

AB - The matrix metalloproteinases (MMPs) are implicated in several activities within the nervous system. Although many functions of abnormally elevated MMPs are undesirable, the discrete expression of particular MMP members can have beneficial roles. We previously found that MMP-9 expressed locally around a demyelinating lesion of the spinal cord of adult mice facilitated remyelination. In the current study, we have addressed whether and how MMPs might be required for myelin formation in normal ontogeny. Using a probe for multiple MMPs and the developing mouse optic nerve, we found two members, MMP-9 and -12, to be upregulated during the period of myelin formation. These MMPs partake in myelinogenesis because myelination in the corpus callosum of MMP-9 and/or MMP-12 null mice was deficient from postnatal days 7 to 14 compared with that of wild-type mice. The deficient myelination was correlated with fewer mature oligodendrocytes, but similar precursor cell numbers, in MMP null animals compared with wild type. Because an important growth factor for oligodendrocyte maturation is insulin-like growth factor-1 (IGF-1), we addressed whether this was involved in the deficient myelination in MMP null mice. Indeed, the addition of IGF-1 normalized the lack of maturation of oligodendrocytes that occurred in cultures from MMP-12 null mice. Furthermore, we determined that IGF binding protein 6 (IGFBP-6), which sequesters IGF-1, was a substrate for MMP processing. Finally, we found IGFBP-6 levels to remain high in MMP-deficient mice. These results reveal a novel function for MMP-9 and -12 in developmental myelination likely through regulating IGF-1 bioavailability.

M3 - Journal article

VL - 26

SP - 2207

EP - 2214

JO - The Journal of Neuroscience

JF - The Journal of Neuroscience

SN - 0270-6474

IS - 8

ER -