title: Impairment of blood-brain barrier is an early event in R6/2 mouse model of Huntington Disease.
abstract: 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.
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Di Pardo
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Amico
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Scalabrì
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pepe
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Castaldo
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Elifani
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Capocci
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: De Sanctis
authors.affiliation: Institute of Biosciences and Bioresources, IBBR, CNR, Napoli, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Comerci
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pompeo
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.|Institute of Genetics and Biophysics "A. Buzzati-Traverso", Naples, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Esposito
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.|Institute of Biosciences and Bioresources, IBBR, CNR, Napoli, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
authors.affiliation: Institute of Biosciences and Bioresources, IBBR, CNR, Napoli, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Crispi
authors.affiliation: IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Maglione
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism; D062507:Claudin-5 / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006816:Huntington Disease / Q000473:pathology*; D051379:Mice; D010539:Permeability
chemical_list: D062507:Claudin-5