Congenital Muscular Dystrophy 1D Causes Matrix Metalloproteinase Activation And Blood-Brain Barrier Impairment

Title:Congenital Muscular Dystrophy 1D Causes Matrix Metalloproteinase Activation And Blood-Brain Barrier Impairment

Volume: 14 Issue: 1

Author(s): Aryadnne L. Schactae, Daphne Palmas, Monique Michels, Jaqueline S. Generoso, Tatiana Barichello, Felipe Dal-Pizzol, Mariz Vainzof and Clarissa M. Comim

Affiliation:

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

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 Large^myd-/- mice in order to understand the physiopathology of brain involvement during the CMD1D process. To this aim, we used adult homozygous Large^myd-/- (mutation in Large), heterozygous Large^myd+/- 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 Large^myd-/- 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.

Cite this article as:

Schactae L. Aryadnne, Palmas Daphne, Michels Monique, Generoso S. Jaqueline, Barichello Tatiana, Dal-Pizzol Felipe, Vainzof Mariz and Comim M. Clarissa, Congenital Muscular Dystrophy 1D Causes Matrix Metalloproteinase Activation And Blood-Brain Barrier Impairment, Current Neurovascular Research 2017; 14 (1) . https://dx.doi.org/10.2174/1567202613666161201204549