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http://hdl.handle.net/2445/178766
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DC Field | Value | Language |
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dc.contributor.author | Vasilopoulou, Foteini | - |
dc.contributor.author | Rodríguez-Arévalo, Sergio | - |
dc.contributor.author | Bagan Polonio, Andrea | - |
dc.contributor.author | Escolano Mirón, Carmen | - |
dc.contributor.author | Griñán Ferré, Christian | - |
dc.contributor.author | Pallàs i Llibería, Mercè, 1964- | - |
dc.date.accessioned | 2021-07-01T12:18:56Z | - |
dc.date.available | 2022-06-22T05:10:27Z | - |
dc.date.issued | 2021-06-22 | - |
dc.identifier.issn | 0007-1188 | - |
dc.identifier.uri | http://hdl.handle.net/2445/178766 | - |
dc.description.abstract | Background and Purpose: The development of effective therapeutic strategies against Alzheimer's disease (AD) remains a challenge. I2 Imidazoline receptors (I2-IR) ligands have a neuroprotective role in AD. Moreover, co-treatment of acetylcholinesterase inhibitors with neuroprotective agents has shown better effects on the prevention of dementia. Here, we assessed the potential therapeutic effect of the I2-IR ligand LSL60101, donepezil, and their combination in 5XFAD mice. Experimental Approach: 5XFAD female mice were treated with low doses of LSL60101 (1 mg kg-1 day-1), donepezil (1 mg kg -1 day-1), and donepezil plus LSL60101 (1+1 mg kg-1 day-1), during 4 weeks per os. Novel object recognition, Morris water maze, open field, elevated plus maze, and three-chamber tests were employed to evaluate the cognitive and behavioural status after treatment. The effects of the treatments on AD-like pathology were assessed with immunohistochemistry, Western blot and qPCR. Key results: Chronic low-dose treatment with LSL60101 and donepezil reversed cognitive deficits and impaired social behaviour. LSL60101 treatment did not affect anxiety-like behaviour in contrast to donepezil. In the 5XFAD brains, LSL60101 and donepezil/LSL60101 treatments decreased Aβ-pathology and Tau hyperphosphorylation, and these alterations were accompanied by reduced microglia marker Iba-1 levels and increased Trem2 gene expression. LSL60601 and donepezil decreased glial fibrillary acidic protein (GFAP) astrocytic marker reactivity. However, only LSL60601 treatment significantly increased the synaptic markers' levels post-density 95 (PSD95) and synaptophysin (SYN). Conclusion and implications: Our results suggest that chronic low dose treatment with selective I2-IR ligands can be an effective treatment for AD and provide insights into combination treatments of symptomatic and disease-modifying drugs. | - |
dc.format.extent | 17 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Blackwell | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1111/bph.15478 | - |
dc.relation.ispartof | British Journal of Pharmacology, 2021, p. 1-17 | - |
dc.relation.uri | https://doi.org/10.1111/bph.15478 | - |
dc.rights | (c) The British Pharmacological Society, 2021 | - |
dc.source | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) | - |
dc.subject.classification | Malaltia d'Alzheimer | - |
dc.subject.classification | Malalties neurodegeneratives | - |
dc.subject.classification | Envelliment | - |
dc.subject.other | Alzheimer's disease | - |
dc.subject.other | Neurodegenerative Diseases | - |
dc.subject.other | Aging | - |
dc.title | Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: A Comparative study with donepezil | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 712953 | - |
dc.date.updated | 2021-07-01T12:18:56Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
Files in This Item:
File | Description | Size | Format | |
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712953.pdf | 3.42 MB | Adobe PDF | View/Open |
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