selective decline of synaptic protein levels in the frontal cortex of female mice deficient in the extracellular metalloproteinase adamts1选择性下降额叶皮质突触蛋白水平的细胞外的雌性老鼠缺乏金属蛋白酶adamts1.pdfVIP

Selective Decline of Synaptic Protein Levels in the Frontal Cortex of Female Mice Deficient in the Extracellular Metalloproteinase ADAMTS1 1 2 2 1 Matthew D. Howell , Antoni X. Torres-Collado , M. Luisa Iruela-Arispe , Paul E. Gottschall * 1 University of Arkansas for Medical Sciences, Department of Pharmacology and Toxicology, Little Rock, Arkansas, United States of America, 2 University of California, Los Angeles, Department of Molecular, Cell, and Developmental Biology, Los Angeles, California, United States of America Abstract The chondroitin sulfate-bearing proteoglycans, also known as lecticans, are a major component of the extracellular matrix (ECM) in the central nervous system and regulate neural plasticity. Growing evidence indicates that endogenous, extracellular metalloproteinases that cleave lecticans mediate neural plasticity by altering the structure of ECM aggregates. The bulk of this in vivo data examined the matrix metalloproteinases, but another metalloproteinase family that cleaves lecticans, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), modulates structural plasticity in vitro, although few in vivo studies have tested this concept. Thus, the purpose of this study was to examine the neurological phenotype of a mouse deficient in ADAMTS1. Adamts1 mRNA was absent in the ADAMTS1 null mouse frontal cortex, but there was no change in the abundance or proteolytic processing of the prominent lecticans brevican and versican V2. However, there was a marked increase in the perinatal lectican neurocan in juvenile ADAMTS1 null female frontal cortex. More prominently, there were declines in synaptic protein levels in the ADAMTS1 null female, but not male, fro