La maladie de Huntington (MH) est une maladie neurod\u00e9g\u00e9n\u00e9rative h\u00e9r\u00e9ditaire qui d\u00e9bute le plus souvent \u00e0 l\u2019\u00e2ge adulte et entra\u00eene la mort apr\u00e8s 10 \u00e0 15 ans d\u2019\u00e9volution. C\u2019est une maladie qui affecte de fa\u00e7on primaire le striatum, une structure c\u00e9r\u00e9brale impliqu\u00e9e dans le contr\u00f4le des mouvements volontaires, mais aussi dans certaines fonctions cognitives\/psychiatriques, notamment la m\u00e9moire des habitudes (par exemple faire du v\u00e9lo, conduire\u2026), la flexibilit\u00e9 comportementale, la motivation\u2026. Dans la MH, les sympt\u00f4mes cognitifs, qui pr\u00e9c\u00e8dent g\u00e9n\u00e9ralement les atteintes motrices d\u2019une dizaine d\u2019ann\u00e9es, ont un impact majeur sur la qualit\u00e9 de vie des patients. Pour autant, la prise en charge m\u00e9dicale de ces sympt\u00f4mes se limite aux th\u00e9rapies cognitives et\/ou comportementales. Le d\u00e9veloppement de traitements plus cibl\u00e9s est entrav\u00e9 par la m\u00e9connaissance des m\u00e9canismes mol\u00e9culaires et cellulaires qui sous-tendent les alt\u00e9rations cognitives sp\u00e9cifiques de la MH. Cette \u00e9tude effectu\u00e9e \u00e0 l\u2019aide de souris mod\u00e8les et de techniques \u00ab\u00a0omics\u00a0\u00bb, permettant d\u2019interroger l\u2019\u00e9tat de la chromatine \u00e0 l\u2019\u00e9chelle du g\u00e9nome, montre que le d\u00e9ficit de m\u00e9moire des habitudes, typique d\u2019un dysfonctionnement du striatum, est associ\u00e9 \u00e0 une diminution des r\u00e9gulations \u00e9pig\u00e9n\u00e9tiques et g\u00e9niques impliqu\u00e9es dans la formation, la consolidation et le rappel de cette m\u00e9moire. Ainsi, chez les animaux t\u00e9moins, le processus mn\u00e9sique s\u2019accompagne d\u2019un remodelage important de l\u2019organisation spatiale de la chromatine, d\u2019une augmentation du degr\u00e9 d\u2019ac\u00e9tylation des histones au niveau de g\u00e8nes responsables de la plasticit\u00e9 c\u00e9r\u00e9brale, et de leur activation transcriptionnelle. Ces r\u00e9gulations, qui impliquent \u00e0 la fois les neurones et les cellules gliales, sont fortement att\u00e9nu\u00e9es chez les souris mod\u00e8les de la MH. L\u2019\u00e9tude permet enfin d\u2019identifier des m\u00e9canismes et cibles nouvelles, notamment l\u2019ac\u00e9tylation de la lysine 9 de l\u2019histone H3 et la voie de signalisation TGF beta, qui pourraient \u00eatre un point de d\u00e9part au d\u00e9veloppement de strat\u00e9gies th\u00e9rapeutiques innovantes.<\/p>\n
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R\u00e9f\u00e9rence :<\/p>\n
Altered activity-regulated H3K9 acetylation at TGF-beta signaling genes during egocentric memory in Huntington’s disease. Alcal\u00e1-Vida R, Lotz C, Brul\u00e9 B, Seguin J, Decraene C, Awada A, Bombardier A, Cosquer B, Pereira de Vasconcelos A, Brouillet E, Cassel JC, Boutillier AL,\u00a0Merienne K. Prog Neurobiol. 2022 Dec;219:102363.<\/p>\n
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L\u00e9gende de l’illustration :<\/p>\n
Chez les souris t\u00e9moins, la formation, la consolidation et le rappel d\u2019une m\u00e9moire proc\u00e9durale (ou m\u00e9moire des habitudes, ici apprendre au travers d\u2019essais r\u00e9p\u00e9t\u00e9s une s\u00e9quence motrice d\u00e9finie pour trouver une plate-forme invisible, localis\u00e9e dans le bras cible) entra\u00eene des r\u00e9ponses \u00e9pig\u00e9n\u00e9tiques dans les neurones et les cellules non neuronales (e.g. les oligodendrocytes) du striatum. Ces r\u00e9ponses, qui mettent en jeu l\u2019ac\u00e9tylation des histones, sont associ\u00e9es \u00e0 l\u2019activation de g\u00e8nes associ\u00e9s aux voies de signalisation du BDNF et du TGF beta, qui sont deux voies majeures de la plasticit\u00e9 cellulaire. Chez les souris Huntington, le d\u00e9ficit de m\u00e9moire proc\u00e9durale s\u2019accompagne d\u2019une alt\u00e9ration de ces r\u00e9ponses \u00e9pig\u00e9n\u00e9tiques essentielles \u00e0 la plasticit\u00e9 c\u00e9r\u00e9brale. Copyright : Karine Merienne et Rafael Alcala Vida ; Cr\u00e9e avec Biorender<\/p>\n
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Contact :<\/p>\n
Karine Merienne, Directrice de recherche CNRS<\/p>\n
karine.merienne@unistra.fr<\/p>\n
Laboratoire de Neurosciences Cognitives et Adaptatives (LNCA), Universit\u00e9 de Strasbourg, Strasbourg 67000, France
\nCentre National de la Recherche Scientifique (CNRS, UMR 7364), Strasbourg 67000, France<\/p>\n
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English summary:<\/em><\/p>\n Huntington\u2019s disease (HD) is a genetic neurodegenerative disease, usually characterized by an adult onset, and leading to death within 10 to 15 years. The disease primarily affects the striatum, a brain structure implicated in the control of voluntary movements, and also in cognitive\/psychiatric functions, including memory of habits (e.g. biking, driving\u2026), cognitive flexibility, motivation\u2026In HD, cognitive symptoms, which generally precede by 10 years motor alterations, have dramatic impact on patients\u2019 quality of life. Medical care of those symptoms only relies on cognitive\/behavioral therapies. The molecular and cellular mechanisms underlying cognitive symptoms in HD remain elusive, which limits the development of specific treatments targeting those symptoms. This study, using \u201comics\u201d approaches to interrogate the chromatin status at genome-wide level, shows that the deficit in habit memory in HD mouse model associates with reduction of epigenetic gene regulations implicated in the formation, consolidation and recall of this memory. In control animals, memory processing is accompanied by major remodeling of spatial organization of the chromatin, increased histone acetylation at genes driving brain plasticity, together with their transcriptional activation. Those regulations, which implicate both neurons and glial cells, are strongly reduced in HD mice. The study also points to new mechanisms and targets, particularly acetylation of histone H3 lysine 9 and TGF beta signaling pathway, which might offer innovative leads to improve HD.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":" La maladie de Huntington (MH) est une maladie neurod\u00e9g\u00e9n\u00e9rative h\u00e9r\u00e9ditaire qui d\u00e9bute le plus souvent \u00e0 l\u2019\u00e2ge adulte et entra\u00eene la mort apr\u00e8s 10 \u00e0 15 ans d\u2019\u00e9volution. C\u2019est une maladie qui affecte de fa\u00e7on primaire le striatum, une structure c\u00e9r\u00e9brale impliqu\u00e9e dans le contr\u00f4le des mouvements volontaires, mais aussi dans certaines fonctions cognitives\/psychiatriques, notamment […]<\/p>\n","protected":false},"author":4,"featured_media":19098,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[25],"tags":[31],"class_list":["post-19064","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized","tag-actualite-en"],"publishpress_future_action":{"enabled":false,"date":"2026-05-13 03:43:02","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category"},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/19064","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/comments?post=19064"}],"version-history":[{"count":1,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/19064\/revisions"}],"predecessor-version":[{"id":19065,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/posts\/19064\/revisions\/19065"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media\/19098"}],"wp:attachment":[{"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/media?parent=19064"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/categories?post=19064"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.neurosciences.asso.fr\/en\/wp-json\/wp\/v2\/tags?post=19064"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}