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.
Keywords: Congenital Muscular Dystrophy type 1D, Large, brain, blood-brain barrier permeability, matrix metalloproteinases.
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