Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/47347
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dc.contributor.authorKESSELS, Sofie-
dc.contributor.authorTRIPPAERS, Chloe-
dc.contributor.authorMERTENS, Melanie-
dc.contributor.authorHAMAD, Ibrahim-
dc.contributor.authorROMBAUT, Ben-
dc.contributor.authorJANSSEN, Art-
dc.contributor.authorRAMANATHAN, Keerthana-
dc.contributor.authorDUWE, Sam-
dc.contributor.authorGharghani, Adelaïde M-
dc.contributor.authorTHEUWIS, Rune-
dc.contributor.authorDELBROEK, Amber-
dc.contributor.authorVANGANSEWINKEL, Tim-
dc.contributor.authorBERDEN, Lisa-
dc.contributor.authorBEEKEN, Jolien-
dc.contributor.authorVANDORMAEL, Patrick-
dc.contributor.authorPoovathingal, Suresh-
dc.contributor.authorVOETS, Thomas-
dc.contributor.authorKLEINEWIETFELD, Markus-
dc.contributor.authorNguyen, Laurent-
dc.contributor.authorAntel, Jack P-
dc.contributor.authorHealy, Luke M-
dc.contributor.authorCowley, Sally A-
dc.contributor.authorIshizuka, Koko-
dc.contributor.authorRIGO, Jean-Michel-
dc.contributor.authorHENDRIX, Jelle-
dc.contributor.authorVANMIERLO, Tim-
dc.contributor.authorDEWACHTER, Ilse-
dc.contributor.authorAlpizar, Yeranddy A-
dc.contributor.authorSawa, Akira-
dc.contributor.authorBRONE, Bert-
dc.date.accessioned2025-09-23T12:06:55Z-
dc.date.available2025-09-23T12:06:55Z-
dc.date.issued2025-
dc.date.submitted2025-09-06T12:28:46Z-
dc.identifier.citationScience advances, 11 (35) (Art N° eadw0128)-
dc.identifier.urihttp://hdl.handle.net/1942/47347-
dc.description.abstractSynaptic dysfunction is a hallmark of neurodevelopmental disorders (NDDs), often linked to genes involved in cytoskeletal regulation. While the role of these genes has been extensively studied in neurons, microglial functions such as phagocytosis are also dependent on cytoskeletal dynamics. We demonstrate that disturbance of actin cytoskeletal regulation in microglia, modeled by genetically impairing the scaffold protein Disrupted-in-Schizophrenia 1 (DISC1), which integrates actin-binding proteins, causes a shift in actin regulatory balance favoring filopodial versus lamellipodial actin organization. The resulting microglia-specific dysregulation of actin dynamics leads to excessive uptake of synaptic proteins. Genetically engineered DISC1-deficient mice show diminished hippocampal excitatory transmission and associated spatial memory deficits. Reintroducing wild-type microglia-like cells via bone marrow transplantation in adult DISC1-deficient mice restores the synaptic function of neurons and rescues cognitive performance. These findings reveal a pivotal role for microglial actin cytoskeletal remodeling in preserving synaptic integrity and cognitive health. Targeting microglial cytoskeletal dynamics may effectively address cognitive impairments associated with NDDs, even in adulthood.-
dc.description.sponsorshipAcknowledgments: We thank M. Jans, Y. Geuens, d. Koenen, J. Mathijs, and W. Roosen for themaintenance of the mouse colonies at BiOMed; R. Beenaerts, P. Bex, and M. P. tulleners for thetechnical assistance with genotyping, cell culture maintenance, and qPcR; and S. Smoldersfor initiating the diSc1 research line in our laboratory and for the foundational contributionsduring the early stages of this work. We thank h. e. de vries (Amsterdam UMc) for providingthe lentiviral lifeAct plasmid. Funding: this work was funded by the Fonds WetenschappelijkOnderzoek (FWO) grants 11e2423n, v420921n, G042121n, G0h3716n, 11A2920n, G080121n,G0G1216, G0A0513, and G0A8l24n; the Bijzonder Onderzoeks Fonds (BOF) BOF21dOc21,BOF21KP06, BOF21GP06, and BOF20KP11; the Bijzonder Onderzoeks Fonds (BOF) AdMiRe(21GP17BOF); the national institute of Mental health grants Mh- 094268, Mh-105660, andMh129480; Odysseus grant G0G1216FWO; the Methusalem Fund Uhasselt BOF22M02-5427G2BOF; and BAeF.-
dc.language.isoen-
dc.publisher-
dc.rights2025 theAuthors, some rightsreserved; exclusivelicensee AmericanAssociation for theAdvancement ofScience. no claim tooriginal U.S.Government Works.distributed under acreative commonsAttribution license 4.0(cc BY).-
dc.subject.otherAnimals-
dc.subject.otherMice-
dc.subject.otherNerve Tissue Proteins-
dc.subject.otherActins-
dc.subject.otherHippocampus-
dc.subject.otherNeurons-
dc.subject.otherMice, Knockout-
dc.subject.otherDisease Models, Animal-
dc.subject.otherActin Cytoskeleton-
dc.subject.otherMicroglia-
dc.subject.otherSynapses-
dc.subject.otherCognitive Dysfunction-
dc.subject.otherCytoskeleton-
dc.subject.otherNeurodevelopmental Disorders-
dc.titleCytoskeletal control in adult microglia is essential to restore neurodevelopmental synaptic and cognitive deficits-
dc.typeJournal Contribution-
dc.identifier.issue35-
dc.identifier.volume11-
local.bibliographicCitation.jcatA1-
dc.description.notesBrône, B (corresponding author), Hasselt Univ, Biomed Res Inst, BIOMED, UHasselt, B-3590 Diepenbeek, Belgium.; Sawa, A (corresponding author), Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA.; Sawa, A (corresponding author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA.; Sawa, A (corresponding author), Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21218 USA.; Sawa, A (corresponding author), Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21218 USA.; Sawa, A (corresponding author), Johns Hopkins Univ, Sch Med, Dept Genet Med, Baltimore, MD 21218 USA.; Sawa, A (corresponding author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.-
dc.description.notesbert.brone@uhasselt.be; asawa1@jhmi.edu-
local.type.refereedRefereed-
local.type.specifiedArticle-
local.bibliographicCitation.artnreadw0128-
dc.identifier.doi10.1126/sciadv.adw0128-
dc.identifier.pmid40880479-
dc.identifier.isi001565146100032-
local.provider.typePubMed-
local.description.affiliation[Kessels, Sofie; Trippaers, Chloe; Mertens, Melanie; Hamad, Ibrahim; Rombaut, Ben; Janssen, Art; Ramanathan, Keerthana; Duwe, Sam; Gharghani, Adelaide M.; Theuwis, Rune; Delbroek, Amber; Vangansewinkel, Tim; Berden, Lisa; Beeken, Jolien; Vandormael, Patrick; Kleinewietfeld, Markus; Rigo, Jean-Michel; Hendrix, Jelle; Vanmierlo, Tim; Dewachter, Ilse; Alpizar, Yeranddy A.; Brone, Bert] Hasselt Univ, Biomed Res Inst, BIOMED, UHasselt, B-3590 Diepenbeek, Belgium.-
local.description.affiliation[Trippaers, Chloe; Ishizuka, Koko; Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21218 USA.-
local.description.affiliation[Hamad, Ibrahim; Kleinewietfeld, Markus] Hasselt Univ VIB, Ctr Inflammat Res IRC, Lab Translat Immunomodulat, B-3590 Diepenbeek, Belgium.-
local.description.affiliation[Rombaut, Ben; Vanmierlo, Tim] Maastricht Univ, Mental Hlth & Neurosci Res Inst, European Grad Sch Neurosci, Dept Psychiat & Neuropsychol,Div Translat Neurosci, Maastricht, Netherlands.-
local.description.affiliation[Ramanathan, Keerthana; Duwe, Sam; Hendrix, Jelle] Hasselt Univ, Biomed Res Inst, Adv Opt Microscopy Ctr, Dynam Bioimaging Lab, Hasselt, Belgium.-
local.description.affiliation[Delbroek, Amber] Univ Mons, Res Inst Biosci, Mechanobiol & Biomat Grp, CIRMAP, B-7000 Mons, Belgium.-
local.description.affiliation[Berden, Lisa] Belgian Nucl Res Ctr SCK CEN, Nucl Med Applicat Inst, Radiobiol Unit, Mol, Belgium.-
local.description.affiliation[Beeken, Jolien; Nguyen, Laurent] ULiege, GIGA Inst, Lab Mol Regulat Neurogenesis, CHU Sart Tilman, Liege, Belgium.-
local.description.affiliation[Vandormael, Patrick; Poovathingal, Suresh] Katholieke Univ Leuven, Leuven Brain Inst, Dept Neurosci, Leuven, Belgium.-
local.description.affiliation[Poovathingal, Suresh; Voets, Thomas] VIB, Ctr Brain & Dis Res, Leuven, Belgium.-
local.description.affiliation[Voets, Thomas] Univ Leuven, Dept Cellular & Mol Med, Lab Ion Channel Res, Leuven, Belgium.-
local.description.affiliation[Voets, Thomas] Univ Leuven, Dept Cellular & Mol Med, TRP Res Platform Leuven TRPLe, Leuven, Belgium.-
local.description.affiliation[Antel, Jack P.; Healy, Luke M.; Cowley, Sally A.] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Quebec City, PQ, Canada.-
local.description.affiliation[Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21218 USA.-
local.description.affiliation[Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21218 USA.-
local.description.affiliation[Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21218 USA.-
local.description.affiliation[Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Genet Med, Baltimore, MD 21218 USA.-
local.description.affiliation[Sawa, Akira] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA.-
local.uhasselt.internationalyes-
item.fulltextWith Fulltext-
item.fullcitationKESSELS, Sofie; TRIPPAERS, Chloe; MERTENS, Melanie; HAMAD, Ibrahim; ROMBAUT, Ben; JANSSEN, Art; RAMANATHAN, Keerthana; DUWE, Sam; Gharghani, Adelaïde M; THEUWIS, Rune; DELBROEK, Amber; VANGANSEWINKEL, Tim; BERDEN, Lisa; BEEKEN, Jolien; VANDORMAEL, Patrick; Poovathingal, Suresh; VOETS, Thomas; KLEINEWIETFELD, Markus; Nguyen, Laurent; Antel, Jack P; Healy, Luke M; Cowley, Sally A; Ishizuka, Koko; RIGO, Jean-Michel; HENDRIX, Jelle; VANMIERLO, Tim; DEWACHTER, Ilse; Alpizar, Yeranddy A; Sawa, Akira & BRONE, Bert (2025) Cytoskeletal control in adult microglia is essential to restore neurodevelopmental synaptic and cognitive deficits. In: Science advances, 11 (35) (Art N° eadw0128).-
item.accessRightsOpen Access-
item.contributorKESSELS, Sofie-
item.contributorTRIPPAERS, Chloe-
item.contributorMERTENS, Melanie-
item.contributorHAMAD, Ibrahim-
item.contributorROMBAUT, Ben-
item.contributorJANSSEN, Art-
item.contributorRAMANATHAN, Keerthana-
item.contributorDUWE, Sam-
item.contributorGharghani, Adelaïde M-
item.contributorTHEUWIS, Rune-
item.contributorDELBROEK, Amber-
item.contributorVANGANSEWINKEL, Tim-
item.contributorBERDEN, Lisa-
item.contributorBEEKEN, Jolien-
item.contributorVANDORMAEL, Patrick-
item.contributorPoovathingal, Suresh-
item.contributorVOETS, Thomas-
item.contributorKLEINEWIETFELD, Markus-
item.contributorNguyen, Laurent-
item.contributorAntel, Jack P-
item.contributorHealy, Luke M-
item.contributorCowley, Sally A-
item.contributorIshizuka, Koko-
item.contributorRIGO, Jean-Michel-
item.contributorHENDRIX, Jelle-
item.contributorVANMIERLO, Tim-
item.contributorDEWACHTER, Ilse-
item.contributorAlpizar, Yeranddy A-
item.contributorSawa, Akira-
item.contributorBRONE, Bert-
crisitem.journal.issn2375-2548-
crisitem.journal.eissn2375-2548-
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