Oligodendrocytes utilize a matrix metalloproteinase, MMP-9, to extend processes along an astrocyte extracellular matrix

Uhm, Joon H.; Dooley, Nora P.; Oh, Luke; Yong, V. Wee

doi:10.1002/(sici)1098-1136(199801)22:1<53::aid-glia5>3.0.co;2-9

Cited by 132 publications

(98 citation statements)

References 53 publications

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“…In particular, oligodendrocyte-derived MMP-9 supports oligodendrogliosis and myelin restoration (Uhm et al 1998;Oh et al 1999;Larsen et al 2003). We previously demonstrated that MPTP treatment of both mice and monkeys induces a prominent oligodendrogliosis concomitant to the inflammatory process here described (Annese et al 2013).…”

Section: Discussionmentioning

confidence: 54%

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

et al. 2014

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Inflammation is a predominant aspect of neurodegenerative diseases, manifested by glia activation and expression of pro-inflammatory mediators. Studies on animal models of Parkinson's disease (PD) suggest that sustained neuroinflammation exacerbates degeneration of the dopaminergic (DA) nigro-striatal pathway. Therefore, insights into the inflammatory mechanisms of PD may help the development of novel therapeutic strategies against this disease. As extracellular matrix metalloproteinases (MMPs) could be major players in the progression of Parkinsonism, we investigated, in the substantia nigra and striatum of mice acutely injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), changes in mRNA expression, protein levels, and cell localization of MMP-9. This protease is mainly neuronal, but early after MPTP injection its mRNA and protein levels, as well as the number of MMP-9-expressing microglia and astrocytes, increase concomitantly to a prominent inflammation. Neuroinflammation and MMP-9+ glia begin to decline within 2 weeks, although protein levels remain higher than control, in association with a partial recovery of DA nigro-striatal circuit. Comparable quantitative studies on MMP-9 knock-out mice, show a significant decrease in both glia activation and loss of DA neurons and fibers, with respect to wild-type. Moreover, in a parallel study on chronically MPTP-injected macaques, we observed that perpetuation of inflammation and high levels of MMP-9 are associated to DA neuron loss. Our data suggest that MMP-9 released by injured neurons favors glia activation; glial cells in turn reinforce their reactive state via autocrine MMP-9 release, contributing to nigro-striatal pathway degeneration. Specific modulation of MMP-9 activity may, therefore, be a strategy to ameliorate harmful inflammatory outcomes in Parkinsonism. © 2014 Springer-Verlag Berlin Heidelberg

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Section: Discussionmentioning

confidence: 54%

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

et al. 2014

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“…However, it is possible that other metalloproteinases have redundant effects and can substitute for the lack of MMP-12 activity as a result of their broad substrate specificity. In this regard, MMP-9 has been implicated previously in OL process extension and increases early during developmental myelination (Uhm et al, 1998;Oh et al, 1999). The finding that MMP-12 null OLs still mature, although in lower numbers, suggests that MMP-12 is not the only MMP member capable of driving this event.…”

Section: Discussionmentioning

confidence: 85%

“…Previous studies from our laboratory have implicated MMPs in the biology of oligodendrocytes (OLs), which are the cells that extend processes in the CNS to contact axons to form myelin. MMP-9 was found to mediate OL process extension in vitro, and MMP-9 expression correlated with myelination in vivo (Uhm et al, 1998;Oh et al, 1999). In correspondence, MMP-9 removed injury-induced deposition of inhibitory NG2 proteoglycan to allow OPCs to mature into myelinating OLs (Larsen et al, 2003).…”

Section: Introductionmentioning

confidence: 92%

The Expression of Matrix Metalloproteinase-12 by Oligodendrocytes Regulates Their Maturation and Morphological Differentiation

Larsen¹,

Yong²

2004

J. Neurosci.

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Matrix metalloproteinases (MMPs) have important roles in many processes of the developing CNS requiring proteolytic activity such as the migration of neuronal precursors, axonal outgrowth, and vascularization. Another developmental event involving proteolysis is myelin formation, whereby the extensive processes elaborated from oligodendrocytes (OLs) enwrap axons. Here we find MMP-12 transcripts to be produced by OLs in much higher levels than other MMP members examined. MMP-12 activity correlated with the ability of OLs to extend processes in vitro, suggesting a role for MMP-12 in the morphological differentiation of OLs. This was corroborated by results that OL lineage cells from MMP-12 null mice were retarded in their ability to differentiate morphologically and that this deficiency was overcome by the exogenous addition of active MMP-12. Finally, the maturation of oligodendrocyte precursor cells (OPCs) to OLs was significantly reduced in cultures from MMP-12 null mice compared with wild-type controls. We conclude that OL lineage cells express MMP-12 during their maturation and that MMP-12 activity has functional involvement both in maturation of OPCs and in the ability of OPCs and OLs to extend processes.

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“…In addition, Planas et al [42] found MMP-2 also in some cortical neurons, and neuronal MMP-2 has also been described in the cerebellum, including the Purkinje neurons [17,[38][39][40]. In vitro studies have shown that MMP-2 activity is produced by astrocytes and microglia [43], oligodendrocytes [44,45] and even neurons [46]. However, it shall be noted that neuronal cultures consist of very immature populations of cells.…”

Section: Mmps In the Brainmentioning

confidence: 99%

Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology of the adult brain

DZWONEK

2004

FEBS Letters

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More than 20 matrix metalloproteinases (MMPs) and four of their endogenous tissue inhibitors (TIMPs) act together to control tightly temporally restricted, focal proteolysis of extracellular matrix. In the neurons of the adult brain several components of the TIMP/MMP system are expressed and are responsive to changes in neuronal activity. Furthermore, functional studies, especially involving blocking of MMP activities, along with the identification of MMP substrates in the brain strongly suggest that this enzymatic system plays an important physiological role in adult brain neurons, possibly being pivotal for neuronal plasticity.

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Oligodendrocytes utilize a matrix metalloproteinase, MMP-9, to extend processes along an astrocyte extracellular matrix

Cited by 132 publications

References 53 publications

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

Metalloproteinase-9 contributes to inflammatory glia activation and nigro-striatal pathway degeneration in both mouse and monkey models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism

The Expression of Matrix Metalloproteinase-12 by Oligodendrocytes Regulates Their Maturation and Morphological Differentiation

Matrix metalloproteinases and their endogenous inhibitors in neuronal physiology of the adult brain

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