title: Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex.
abstract: BACKGROUND
  Brevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in the central nervous system (CNS) and is thought to stabilize synapses and inhibit neural plasticity and as such, neuritic or synaptic remodeling would be less likely to occur in regions with intact and abundant, lectican-containing, ECM complexes. Neural plasticity may occur more readily when these ECM complexes are broken down by endogenous proteases, the ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs), that selectively cleave the lecticans. The purpose of these experiments was to determine whether the production of brevican or the ADAMTS-cleaved fragments of brevican were altered after deafferentation and reinnervation of the dentate gyrus via entorhinal cortex lesion (ECL).
  
  
  RESULTS
  In the C57Bl6J mouse, synaptic density in the molecular layer of the dentate gyrus, as measured by synaptophysin levels in ELISA, was significantly attenuated 2 days (nearly 50% of contralateral) and 7 days after lesion and returned to levels not different from the contralateral region at 30 days. Immunoreactive brevican in immunoblot was elevated 2 days after lesion, whereas there was a significant increase in the proteolytic product at 7, but not 30 days post-lesion. ADAMTS activity, estimated using the ratio of the specific ADAMTS-derived brevican fragment and intact brevican levels was increased at 7 days, but was not different from the contralateral side at 2 or 30 days after deafferentation.
  
  
  CONCLUSIONS
  These findings indicate that ADAMTS activity in the dentate outer molecular layer (OML) is elevated during the initial synaptic reinnervation period (7 days after lesion). Therefore, proteolytic processing of brevican appears to be a significant extracellular event in the remodeling of the dentate after EC lesion, and may modulate the process of sprouting and/or synaptogenesis.
authors.affiliation: Department of Pharmacology and Therapeutics, University of South Florida College of Medicine, Tampa, Florida 33612-4799, USA. jmayer1@hsc.usf.edu
authors.forename: Joanne
authors.initials: J
authors.lastname: Mayer
authors.forename: Michelle G
authors.initials: MG
authors.lastname: Hamel
authors.forename: Paul E
authors.initials: PE
authors.lastname: Gottschall
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D020816:Amino Acid Motifs; D000818:Animals; D058581:Brevican; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism*; D018891:Dentate Gyrus / Q000187:drug effects / Q000201:enzymology*; D019483:Disintegrins / Q000378:metabolism; D018728:Entorhinal Cortex / Q000187:drug effects / Q000201:enzymology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006868:Hydrolysis; D037181:Lectins, C-Type / Q000378:metabolism*; D008297:Male; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010447:Peptide Hydrolases / Q000378:metabolism*; D019699:Thrombospondins / Q000737:chemistry / Q000378:metabolism
chemical_list: C553057:Bcan protein, mouse; D058581:Brevican; D011508:Chondroitin Sulfate Proteoglycans; D019483:Disintegrins; D018690:Excitatory Amino Acid Agonists; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D019699:Thrombospondins; D045726:Metalloproteases; D010447:Peptide Hydrolases; D051722:ADAM Proteins