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Title: I2 imidazoline receptor modulation protects aged SAMP8 mice against cognitive decline by suppressing the calcineurin pathway
Author: Vasilopoulou, Foteini
Griñán Ferré, Christian
Rodríguez-Arévalo, Sergio
Bagan Polonio, Andrea
Escolano Mirón, Carmen
Pallàs i Llibería, Mercè, 1964-
Keywords: Demència
Envelliment cerebral
Malaltia d'Alzheimer
Malalties neurodegeneratives
Aging brain
Alzheimer's disease
Neurodegenerative Diseases
Issue Date: 31-Oct-2020
Publisher: Springer Nature
Abstract: Brain aging and dementia are current problems that must be solved. The levels of imidazoline 2 receptors (I2-IRs) are increased in the brain in Alzheimer's disease (AD) and other neurodegenerative diseases. We tested the action of the specific and selective I2-IR ligand B06 in a mouse model of accelerated aging and AD, the senescence-accelerated mouse prone 8 (SAMP8) model. Oral administration of B06 for 4 weeks improved SAMP8 mouse behavior and cognition and reduced AD hallmarks, oxidative stress, and apoptotic and neuroinflammation markers. Likewise, B06 regulated glial excitatory amino acid transporter 2 and N-methyl-D aspartate 2A and 2B receptor subunit protein levels. Calcineurin (CaN) is a phosphatase that controls the phosphorylation levels of cAMP response element-binding (CREB), apoptotic mediator BCL-2-associated agonist of cell death (BAD) and GSK3β, among other molecules. Interestingly, B06 was able to reduce the levels of the CaN active form (CaN A). Likewise, CREB phosphorylation, BAD gene expression, and other factors were modified after B06 treatment. Moreover, phosphorylation of a target of CaN, nuclear factor of activated Tcells, cytoplasmic 1 (NFATC1), was increased in B06- treated mice, impeding the transcription of genes related to neuroinflammation and neural plasticity. In summary, this I2 imidazoline ligand can exert its beneficial effects on age-related conditions by modulating CaN pathway action and affecting several molecular pathways, playing a neuroprotective role in SAMP8
Note: Versió postprint del document publicat a:
It is part of: Geroscience, 2020
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ISSN: 2509-2715
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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