Show simple item record

dc.contributor.authorBirolini, Giulia
dc.contributor.authorValenza, Marta
dc.contributor.authorDi Paolo, Eleonora
dc.contributor.authorVezzoli, Elena
dc.contributor.authorTalpo, Francesca
dc.contributor.authorManiezzi, Claudia
dc.contributor.authorCaccia, Claudio
dc.contributor.authorLeoni, Valerio
dc.contributor.authorTaroni, Franco
dc.contributor.authorBocchi, Vittoria D
dc.contributor.authorConforti, Paola
dc.contributor.authorSogne, Elisa
dc.contributor.authorPetricca, Lara
dc.contributor.authorCariulo, Cristina
dc.contributor.authorVerani, Margherita
dc.contributor.authorCaricasole, Andrea
dc.contributor.authorFalqui, Andrea
dc.contributor.authorBiella, Gerardo
dc.contributor.authorCattaneo, Elena
dc.date.accessioned2020-09-28T10:45:15Z
dc.date.available2020-09-28T10:45:15Z
dc.date.issued2020-09-22
dc.date.submitted2020-04-15
dc.identifier.citationBirolini, G., Valenza, M., Di Paolo, E., Vezzoli, E., Talpo, F., Maniezzi, C., … Cattaneo, E. (2020). Striatal infusion of cholesterol promotes dose-dependent behavioral benefits and exerts disease-modifying effects in Huntington’s disease mice. EMBO Molecular Medicine. doi:10.15252/emmm.202012519
dc.identifier.issn1757-4676
dc.identifier.issn1757-4684
dc.identifier.pmid32959531
dc.identifier.doi10.15252/emmm.202012519
dc.identifier.urihttp://hdl.handle.net/10754/665339
dc.description.abstractA variety of pathophysiological mechanisms are implicated in Huntington's disease (HD). Among them, reduced cholesterol biosynthesis has been detected in the HD mouse brain from pre-symptomatic stages, leading to diminished cholesterol synthesis, particularly in the striatum. In addition, systemic injection of cholesterol-loaded brain-permeable nanoparticles ameliorates synaptic and cognitive function in a transgenic mouse model of HD. To identify an appropriate treatment regimen and gain mechanistic insights into the beneficial activity of exogenous cholesterol in the HD brain, we employed osmotic mini-pumps to infuse three escalating doses of cholesterol directly into the striatum of HD mice in a continuous and rate-controlled manner. All tested doses prevented cognitive decline, while amelioration of disease-related motor defects was dose-dependent. In parallel, we found morphological and functional recovery of synaptic transmission involving both excitatory and inhibitory synapses of striatal medium spiny neurons. The treatment also enhanced endogenous cholesterol biosynthesis and clearance of mutant Huntingtin aggregates. These results indicate that cholesterol infusion to the striatum can exert a dose-dependent, disease-modifying effect and may be therapeutically relevant in HD.
dc.publisherEMBO
dc.relation.urlhttps://onlinelibrary.wiley.com/doi/10.15252/emmm.202012519
dc.rightsThis is an open access article under theterms of the Creative Commons Attribution 4.0License, which permits use, distribution and reproduc-tion in any medium, provided the original work isproperly cited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleStriatal infusion of cholesterol promotes dose-dependent behavioral benefits and exerts disease-modifying effects in Huntington's disease mice
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.identifier.journalEMBO Molecular Medicine
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Biosciences University of Milan Milan Italy
dc.contributor.institutionIstituto Nazionale di Genetica Molecolare “Romeo ed Enrica Invernizzi” Milan Italy
dc.contributor.institutionDepartment of Biology and Biotechnologies University of Pavia Pavia Italy
dc.contributor.institutionUnit of Medical Genetics and Neurogenetics Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta Milan Italy
dc.contributor.institutionSchool of Medicine and Surgery Monza and Laboratory of Clinical Pathology Hospital of Desio ASST-Monza University of Milano-Bicocca Milan Italy
dc.contributor.institutionNeuroscience Unit Translational and Discovery Research Department IRBM S.p.A Rome Italy
kaust.personSogne, Elisa
kaust.personFalqui, Andrea
dc.date.accepted2020-08-26
dc.identifier.eid2-s2.0-85091258098
refterms.dateFOA2020-09-28T10:46:16Z
dc.date.published-online2020-09-22
dc.date.published-print2020-10-07


Files in this item

Thumbnail
Name:
emmm.202012519 (1).pdf
Size:
10.85Mb
Format:
PDF
Description:
Published version

This item appears in the following Collection(s)

Show simple item record

This is an open access article under theterms of the Creative Commons Attribution 4.0License, which permits use, distribution and reproduc-tion in any medium, provided the original work isproperly cited.
Except where otherwise noted, this item's license is described as This is an open access article under theterms of the Creative Commons Attribution 4.0License, which permits use, distribution and reproduc-tion in any medium, provided the original work isproperly cited.