title: Congenital Muscular Dystrophy 1D Causes Matrix Metalloproteinase Activation And Blood-Brain Barrier Impairment.
abstract: Congenital Muscular Dystrophy type 1D (CMD1D) is characterized by an abnormal glycosylation of α-DG (α-dystroglycan) and is associated to the central nervous system (CNS) abnormalities such as cognitive impairment. The purpose of the research was to evaluate the blood-brain barrier permeability (BBB) permeability and matrix metalloproteinases (MMP) -2 and -9 in adult Largemyd-/- mice in order to understand the physiopathology of brain involvement during the CMD1D process. To this aim, we used adult homozygous Largemyd-/- (mutation in Large), heterozygous Largemyd+/- as well as wild-type (C57BL/6) mice. The animals were submitted to the evaluation of BBB permeability and MMP-2 and MMP-9 in striatum, hippocampus and cerebral cortex. There was an increase in BBB permeability in the hippocampus and striatum associated with an increase in the protein levels of MMP-2 in the cerebral cortex and striatum and MMP-9 in the hippocampus in adult Largemyd-/- mice. Our results suggest that the pathophysiologic processes can be associated to the action of MMPs and BBB disruption and that the BBB breakdown is relevant to the perpetuation of brain inflammation and can be related to brain dysfunction observed in CMD1D patients.
authors.forename: Aryadnne L
authors.initials: AL
authors.lastname: Schactae
authors.forename: Daphne
authors.initials: D
authors.lastname: Palmas
authors.forename: Monique
authors.initials: M
authors.lastname: Michels
authors.forename: Jaqueline S
authors.initials: JS
authors.lastname: Generoso
authors.forename: Tatiana
authors.initials: T
authors.lastname: Barichello
authors.forename: Felipe
authors.initials: F
authors.lastname: Dal-Pizzol
authors.forename: Mariz
authors.initials: M
authors.lastname: Vainzof
authors.affiliation: Research Group of Experimental Neuropathology, Laboratory of Experimental Neuroscience. University of South Santa Catarina, Postgraduate Program in Health Sciences, Palhoça, SC, Brazil.
authors.forename: Clarissa M
authors.initials: CM
authors.lastname: Comim
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000201:enzymology*; D001921:Brain / Q000002:abnormalities* / Q000201:enzymology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006624:Hippocampus / Q000378:metabolism; D008607:Intellectual Disability / Q000201:enzymology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009136:Muscular Dystrophies / Q000201:enzymology*; D010539:Permeability
chemical_list: D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Congenital Muscular Dystrophy type 1D; Large; blood-brain barrier permeability; brain; matrix metalloproteinases