Elevated MMP-9 and degradation of perineuronal nets in cerebrocortical multiple sclerosis plaques

E Gray, TL Thomas, S Betmouni, N Scolding, S Love

Research output: Contribution to journalArticle (Academic Journal)

22 Citations (Scopus)

Abstract

Matrix metalloproteinases (MMPs) degrade extracellular matrix; MMP activity, particularly of MMP-9, is elevated in the white matter in multiple sclerosis (MS) patients. The cerebral cortical extracellular matrix includes perineuronal nets (PNs) that surround parvalbumin-positive neurons (PV-positive neurons) and are important for their function. We measured active and total MMP-9 levels in postmortem homogenates of demyelinated and nondemyelinated cerebral cortical regions from 9MS and 7 control cases and assessed Wisteria floribunda agglutin (WFA)-positive PNs in paraffin sections from 15 MS and 6 controls and PV-positive neurons in sections from 26 MS and 6 controls. Active MMP-9 levels were higher in demyelinated than in nondemyelinated or control cortex (p < 0.05). The area fraction positive for WFA was lower in demyelinated than nondemyelinated MS or control cortex; the latter difference was significant (p < 0.05). Most PV-positive neurons in demyelinated but not intact cortex lackeda PN, and some showed perikaryal phosphorylated neurofilament protein accumulation. Loss of WFA-labeled PNs was not associated with reduced PV-positive neurons numbers. Thus, elevated MMP-9 in cortical plaques is associated with loss of PNs; PV-positive neurons are preserved but show abnormal neurofilament accumulations. Matrix metalloproteinase-mediated degradation of PNs in cortical plaques may, therefore, contribute to neuronal dysfunction and degeneration in MS patients.
Translated title of the contributionElevated MMP-9 and degradation of perineuronal nets in cerebrocortical multiple sclerosis plaques
Original languageEnglish
Pages (from-to)888 - 899
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume67
Issue number9
DOIs
Publication statusPublished - Sep 2008

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