Open AccessImpairment of blood-brain barrier is an early event in R6/2 mouse model of Huntington Disease
Author(s) -
Alba Di Pardo,
Enrico Amico,
Francesco Scalabrì,
Giuseppe Pepe,
Salvatore Castaldo,
Francesca Elifani,
Luca Capocci,
Claudia De Sanctis,
Laura Comerci,
Francesco Pompeo,
Maurizio D’Esposito,
Stefania Filosa,
Stefania Crispi,
Vittorio Maglione
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep41316
Subject(s) - blood–brain barrier , disease , huntington's disease , neuroscience , medicine , pathological , tight junction , brain function , biology , central nervous system , pathology , microbiology and biotechnology
Blood-brain barrier (BBB) breakdown, due to the concomitant disruption of the tight junctions (TJs), normally required for the maintenance of BBB function, and to the altered transport of molecules between blood and brain and vice-versa, has been suggested to significantly contribute to the development and progression of different brain disorders including Huntington’s disease (HD). Although the detrimental consequence the BBB breakdown may have in the clinical settings, the timing of its alteration remains elusive for many neurodegenerative diseases. In this study we demonstrate for the first time that BBB disruption in HD is not confined to established symptoms, but occurs early in the disease progression. Despite the obvious signs of impaired BBB permeability were only detectable in concomitance with the onset of the disease, signs of deranged TJs integrity occur precociously in the disease and precede the onset of overt symptoms. To our perspective this finding may add a new dimension to the horizons of pathological mechanisms underlying this devastating disease, however much remains to be elucidated for understanding how specific BBB drug targets can be approached in the future.