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http://hdl.handle.net/2445/164884
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DC Field | Value | Language |
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dc.contributor.author | Vasilopoulou, Foteini | - |
dc.contributor.author | Bagan Polonio, Andrea | - |
dc.contributor.author | Rodríguez-Arévalo, Sergio | - |
dc.contributor.author | Escolano Mirón, Carmen | - |
dc.contributor.author | Griñán Ferré, Christian | - |
dc.contributor.author | Pallàs i Llibería, Mercè, 1964- | - |
dc.date.accessioned | 2020-06-09T08:33:19Z | - |
dc.date.available | 2020-06-09T08:33:19Z | - |
dc.date.issued | 2020-05-22 | - |
dc.identifier.issn | 1999-4923 | - |
dc.identifier.uri | http://hdl.handle.net/2445/164884 | - |
dc.description.abstract | Behavioural and Psychological Symptoms of Dementia (BPSD), including fear-anxiety- and depressive-like behaviour, are present in Alzheimer's disease (AD), together with memory decline. I2-imidazoline receptors (I2-IRs) have been associated with neuropsychiatric and neurodegenerative disorders, further, I2-IR ligands have demonstrated a neuroprotective role in the central nervous system (CNS). In this study, we assessed the effect of the I2-IR ligand MCR5 on both cognitive and non-cognitive symptoms in the Senescence accelerated mice prone 8 (SAMP8) mouse model. Oral administration of I2-IR ligand MCR5 (5mg/kg/day for four weeks) in 10-month SAMP8 mice ameliorated both BPSD-like phenotype and cognitive decline by attenuating depressive-like behaviour, reducing fear-anxiety-like behaviour and improving cognitive performance using different tasks. Interaction of I2-IR ligand MCR5 with serotoninergic system did not account for behavioral or cognitive improvement, although changes in molecular pathways underlying depression and anxiety phenotype were observed. MCR5 increased levels of p-AKT, phosphorylated Glycogen synthase kinase 3 β (GSK3β) at Ser9 and phosphorylated mammalian target of rapamycin complex 1 (mTORC1) levels in SAMP8 treated mice compared to SAMP8 control. Moreover, MCR5 treatment altered NMDA2B phosphorylation, and decreased the protein levels of phosphorylated Cyclin-Dependent Kinase 5 (p-CDK5) and dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa phosphorylated at Thr75 (p-DARPP32), with a parallel increase in PKA and p-CREB levels. Consistent with these changes MCR5 attenuated neuroinflammation by decreasing expression of pro-inflammatory markers such as Tumor necrosis factor-alpha (Tnf-α), Interleukin 1β (Il-1β), Interleukin 6 (Il-6), and promoted synaptic plasticity by increasing levels of Postsynaptic density protein 95 (PSD95) as well as ameliorating Tropomyosin-related kinase B (TrkB) and Nerve growth factor receptor (NGFR) signalling. Collectively, these results increase the potential of highly selective I2-IR ligands as therapeutic agents in age-related BPSD and cognitive alterations. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | MDPI | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3390/pharmaceutics12050475 | - |
dc.relation.ispartof | Pharmaceutics, 2020, vol. 12, num. 5, p. E475 | - |
dc.relation.uri | https://doi.org/10.3390/pharmaceutics12050475 | - |
dc.rights | cc-by (c) Vasilopoulou, Foteini et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es | - |
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.classification | Ratolins (Animals de laboratori) | - |
dc.subject.other | Alzheimer's disease | - |
dc.subject.other | Neurodegenerative Diseases | - |
dc.subject.other | Aging | - |
dc.subject.other | Mice (Laboratory animals) | - |
dc.title | Amelioration of BPSD-like phenotype and cognitive decline in SAMP8 mice model accompanied by molecular changes after treatment with I2-imidazoline receptor ligand MCR5 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 701100 | - |
dc.date.updated | 2020-06-09T08:33:19Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32456135 | - |
Appears in Collections: | Articles publicats en revistes (Institut de Biomedicina (IBUB)) Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) |
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701100.pdf | 3.16 MB | Adobe PDF | View/Open |
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