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http://hdl.handle.net/1942/43369
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DC Field | Value | Language |
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dc.contributor.author | ROMBAUT, Ben | - |
dc.contributor.author | SCHEPERS, Melissa | - |
dc.contributor.author | TIANE, Assia | - |
dc.contributor.author | MUSSEN, Femke | - |
dc.contributor.author | KOOLE, Lisa | - |
dc.contributor.author | KESSELS, Sofie | - |
dc.contributor.author | TRIPPAERS, Chloe | - |
dc.contributor.author | JACOBS, Ruben | - |
dc.contributor.author | WOUTERS, Kristiaan | - |
dc.contributor.author | WILLEMS, Emily | - |
dc.contributor.author | VAN VEGGEL, Lieve | - |
dc.contributor.author | KOULOUSAKIS, Philippos | - |
dc.contributor.author | DELUYKER, Dorien | - |
dc.contributor.author | BITO, Virginie | - |
dc.contributor.author | Prickaerts, Jos | - |
dc.contributor.author | WENS, Inez | - |
dc.contributor.author | BRONE, Bert | - |
dc.contributor.author | van den Hove, Daniel L. A. | - |
dc.contributor.author | VANMIERLO, Tim | - |
dc.date.accessioned | 2024-07-15T07:32:48Z | - |
dc.date.available | 2024-07-15T07:32:48Z | - |
dc.date.issued | 2024 | - |
dc.date.submitted | 2024-07-15T06:29:18Z | - |
dc.identifier.citation | Cells, 13 (12) (Art N° 1000) | - |
dc.identifier.uri | http://hdl.handle.net/1942/43369 | - |
dc.description.abstract | Microglia activity can drive excessive synaptic loss during the prodromal phase of Alzheimer's disease (AD) and is associated with lowered cyclic adenosine monophosphate (cAMP) due to cAMP phosphodiesterase 4B (PDE4B). This study aimed to investigate whether long-term inhibition of PDE4B by A33 (3 mg/kg/day) can prevent synapse loss and its associated cognitive decline in APPswe/PS1dE9 mice. This model is characterized by a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9 (dE9), both under the control of the mouse prion protein promoter. The effects on cognitive function of prolonged A33 treatment from 20 days to 4 months of age, was assessed at 7-8 months. PDE4B inhibition significantly improved both the working and spatial memory of APPswe/PSdE9 mice after treatment ended. At the cellular level, in vitro inhibition of PDE4B induced microglial filopodia formation, suggesting that regulation of PDE4B activity can counteract microglia activation. Further research is needed to investigate if this could prevent microglia from adopting their 'disease-associated microglia (DAM)' phenotype in vivo. These findings support the possibility that PDE4B is a potential target in combating AD pathology and that early intervention using A33 may be a promising treatment strategy for AD. | - |
dc.description.sponsorship | This research was funded by Fonds Wetenschappelijk Onderzoek (FWO), grant numbers 11A2920N, 11E2423N, and G042121N, and the APC was funded by FWO (G042121N). We also received funding from BAEF. | - |
dc.language.iso | en | - |
dc.publisher | MDPI | - |
dc.rights | 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). | - |
dc.subject.other | Alzheimer's disease | - |
dc.subject.other | cyclic nucleotide phosphodiesterases type 4B | - |
dc.subject.other | synapse | - |
dc.subject.other | microglia | - |
dc.subject.other | cognition | - |
dc.title | Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice | - |
dc.type | Journal Contribution | - |
dc.identifier.issue | 12 | - |
dc.identifier.volume | 13 | - |
local.format.pages | 21 | - |
local.bibliographicCitation.jcat | A1 | - |
dc.description.notes | Vanmierlo, T (corresponding author), Hasselt Univ, Biomed Res Inst, Fac Med & Life Sci, Dept Neurosci, B-3500 Hasselt, Belgium.; Vanmierlo, T (corresponding author), Maastricht Univ, Sch Mental Hlth & Neurosci MHeNS, Dept Psychiat & Neuropsychol, NL-6229 ER Maastricht, Netherlands.; Vanmierlo, T (corresponding author), Univ MS Ctr UMSC Hasselt, B-3900 Pelt, Belgium. | - |
dc.description.notes | ben.rombaut@uhasselt.be; m.schepers@maastrichtuniversity.nl; | - |
dc.description.notes | a.tiane@maastrichtuniversity.nl; femke.mussen@uhasselt.be; | - |
dc.description.notes | lisa.koole@maastrichtuniversity.nl; sofie.kessels@uhasselt.be; | - |
dc.description.notes | chloe.trippaers@uhasselt.be; ruben.jacobs@maastrichtuniversity.nl; | - |
dc.description.notes | kristiaan.wouters@maastrichtuniversity.nl; emily.willems@uhasselt.be; | - |
dc.description.notes | lieve.vanveggel@uhasselt.be; p.koulousakis@maastrichtuniversity.nl; | - |
dc.description.notes | dorien.deluyker@uhasselt.be; virginie.bito@uhasselt.be; | - |
dc.description.notes | jos.prickaerts@gmail.com; inez.wens@uhasselt.be; bert.brone@uhasselt.be; | - |
dc.description.notes | d.vandenhove@maastrichtuniversity.nl; | - |
dc.description.notes | t.vanmierlo@maastrichtuniversity.nl | - |
local.publisher.place | ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND | - |
local.type.refereed | Refereed | - |
local.type.specified | Article | - |
local.bibliographicCitation.artnr | 1000 | - |
dc.identifier.doi | 10.3390/cells13121000 | - |
dc.identifier.pmid | 38920631 | - |
dc.identifier.isi | 001254548200001 | - |
dc.contributor.orcid | van Veggel, Lieve/0000-0001-7725-8710; Vanmierlo, | - |
dc.contributor.orcid | Tim/0000-0003-2912-0578 | - |
local.provider.type | wosris | - |
local.description.affiliation | [Rombaut, Ben; Schepers, Melissa; Tiane, Assia; Mussen, Femke; Koole, Lisa; Kessels, Sofie; Trippaers, Chloe; Jacobs, Ruben; Willems, Emily; van Veggel, Lieve; Koulousakis, Philippos; Wens, Inez; Brone, Bert; Vanmierlo, Tim] Hasselt Univ, Biomed Res Inst, Fac Med & Life Sci, Dept Neurosci, B-3500 Hasselt, Belgium. | - |
local.description.affiliation | [Rombaut, Ben; Schepers, Melissa; Tiane, Assia; Mussen, Femke; Koole, Lisa; Willems, Emily; van Veggel, Lieve; Koulousakis, Philippos; Prickaerts, Jos; Wens, Inez; van den Hove, Daniel L. A.; Vanmierlo, Tim] Maastricht Univ, Sch Mental Hlth & Neurosci MHeNS, Dept Psychiat & Neuropsychol, NL-6229 ER Maastricht, Netherlands. | - |
local.description.affiliation | [Schepers, Melissa; Tiane, Assia; van Veggel, Lieve; Wens, Inez; Vanmierlo, Tim] Univ MS Ctr UMSC Hasselt, B-3900 Pelt, Belgium. | - |
local.description.affiliation | [Mussen, Femke] Hasselt Univ, Biomed Res Inst, Dept Immunol & Infect, B-3500 Hasselt, Belgium. | - |
local.description.affiliation | [Trippaers, Chloe] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. | - |
local.description.affiliation | [Wouters, Kristiaan] Maastricht Univ, Med Ctr MUMC, Dept Internal Med, NL-6229 ER Maastricht, Netherlands. | - |
local.description.affiliation | [Wouters, Kristiaan] Maastricht Univ, Cardiovasc Res Inst Maastricht CARIM, NL-6229 ER Maastricht, Netherlands. | - |
local.description.affiliation | [Deluyker, Dorien; Bito, Virginie] UHasselt, Cardio & Organ Syst COST, BIOMED, Agoralaan, B-3590 Diepenbeek, Belgium. | - |
local.description.affiliation | [van den Hove, Daniel L. A.] Univ Wurzburg, Dept Psychiat Psychosomat & Psychotherapy, D-97070 Wurzburg, Germany. | - |
local.uhasselt.international | yes | - |
item.accessRights | Open Access | - |
item.contributor | ROMBAUT, Ben | - |
item.contributor | SCHEPERS, Melissa | - |
item.contributor | TIANE, Assia | - |
item.contributor | MUSSEN, Femke | - |
item.contributor | KOOLE, Lisa | - |
item.contributor | KESSELS, Sofie | - |
item.contributor | TRIPPAERS, Chloe | - |
item.contributor | JACOBS, Ruben | - |
item.contributor | WOUTERS, Kristiaan | - |
item.contributor | WILLEMS, Emily | - |
item.contributor | VAN VEGGEL, Lieve | - |
item.contributor | KOULOUSAKIS, Philippos | - |
item.contributor | DELUYKER, Dorien | - |
item.contributor | BITO, Virginie | - |
item.contributor | Prickaerts, Jos | - |
item.contributor | WENS, Inez | - |
item.contributor | BRONE, Bert | - |
item.contributor | van den Hove, Daniel L. A. | - |
item.contributor | VANMIERLO, Tim | - |
item.fullcitation | ROMBAUT, Ben; SCHEPERS, Melissa; TIANE, Assia; MUSSEN, Femke; KOOLE, Lisa; KESSELS, Sofie; TRIPPAERS, Chloe; JACOBS, Ruben; WOUTERS, Kristiaan; WILLEMS, Emily; VAN VEGGEL, Lieve; KOULOUSAKIS, Philippos; DELUYKER, Dorien; BITO, Virginie; Prickaerts, Jos; WENS, Inez; BRONE, Bert; van den Hove, Daniel L. A. & VANMIERLO, Tim (2024) Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice. In: Cells, 13 (12) (Art N° 1000). | - |
item.fulltext | With Fulltext | - |
crisitem.journal.eissn | 2073-4409 | - |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe_PS1dE9 Mice.pdf | Published version | 2.66 MB | Adobe PDF | View/Open |
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