Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/43369
Title: | Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice | Authors: | 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 |
Issue Date: | 2024 | Publisher: | MDPI | Source: | Cells, 13 (12) (Art N° 1000) | 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. | 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. ben.rombaut@uhasselt.be; m.schepers@maastrichtuniversity.nl; a.tiane@maastrichtuniversity.nl; femke.mussen@uhasselt.be; lisa.koole@maastrichtuniversity.nl; sofie.kessels@uhasselt.be; chloe.trippaers@uhasselt.be; ruben.jacobs@maastrichtuniversity.nl; kristiaan.wouters@maastrichtuniversity.nl; emily.willems@uhasselt.be; lieve.vanveggel@uhasselt.be; p.koulousakis@maastrichtuniversity.nl; dorien.deluyker@uhasselt.be; virginie.bito@uhasselt.be; jos.prickaerts@gmail.com; inez.wens@uhasselt.be; bert.brone@uhasselt.be; d.vandenhove@maastrichtuniversity.nl; t.vanmierlo@maastrichtuniversity.nl |
Keywords: | Alzheimer's disease;cyclic nucleotide phosphodiesterases type 4B;synapse;microglia;cognition | Document URI: | http://hdl.handle.net/1942/43369 | ISSN: | 2073-4409 | e-ISSN: | 2073-4409 | DOI: | 10.3390/cells13121000 | ISI #: | 001254548200001 | 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/). | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe_PS1dE9 Mice.pdf | Published version | 2.66 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.