NDLI: The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain.

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The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain.

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The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Vo, Tam Carulli, Daniela Ehlert, Erich M. E. Kwok, Jessica C. F. Dick, Gunnar Mecollari, Vasil Moloney, Elizabeth B. Neufeld, Gera de Winter, Fred Fawcett, James W. Verhaagen, Joost
Description	Country affiliation: Netherlands Author Affiliation: Vo T ( Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.)
Abstract	In the adult rodent brain, subsets of neurons are surrounded by densely organised extracellular matrix called perineuronal nets (PNNs). PNNs consist of hyaluronan, tenascin-R, chondroitin sulphate proteoglycans (CSPGs), and the link proteins Crtl1 and Bral2. PNNs restrict plasticity at the end of critical periods and can be visualised with Wisteria floribunda agglutinin (WFA). Using a number of antibodies raised against the different regions of semaphorin3A (Sema3A) we demonstrate that this secreted chemorepulsive axon guidance protein is localised to WFA-positive PNNs around inhibitory interneurons in the cortex and several other PNN-bearing neurons throughout the brain and co-localises with aggrecan, versican, phosphacan and tenascin-R. Chondroitinase ABC (ChABC) was injected in the cortex to degrade glycosaminoglycans (GAGs) from the CSPGs, abolishing WFA staining of PNNs around the injection site. Sema3A-positive nets were no longer observed in the area devoid of WFA staining. In mice lacking the link protein Crtl1 in the CNS only vestigial PNNs are present, and in these mice there were no Sema3A-positive PNN structures. A biochemical analysis shows that Sema3A protein binds with high-affinity to CS-GAGs and aggrecan and versican extracted from PNNs in the adult rat brain, and a significant proportion of Sema3A is retrieved in brain extracts that are enriched in PNN-associated GAGs. The Sema3A receptor components PlexinA1 and A4 are selectively expressed by inhibitory interneurons in the cortex that are surrounded by Sema3A positive PNNs. We conclude that the chemorepulsive axon guidance molecule Sema3A is present in PNNs of the adult rodent brain, bound to the GAGs of the CSPGs. These observations suggest a novel concept namely that chemorepulsive axon guidance molecules like Sema3A may be important functional attributes of PNNs in the adult brain.
File Format	HTM / HTML
ISSN	10447431
Volume Number	56
e-ISSN	10959327
Journal	Molecular and Cellular Neuroscience
Language	English
Publisher	Elsevier
Publisher Date	2013-09-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Cell Biology Discipline Molecular Biology Discipline Neurology Cerebral Cortex Metabolism Extracellular Matrix Semaphorin-3a Aggrecans Animals Cytology Extracellular Matrix Proteins Genetics Glycosaminoglycans Hek293 Cells Humans Interneurons Mice Mice, Inbred C57bl Protein Binding Proteoglycans Rats Rats, Sprague-dawley Rats, Wistar Versicans Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Cellular and Molecular Neuroscience

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