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Behavioral and Cognitive Improvement Induced by Novel Imidazoline I2 Receptor Ligands in Female SAMP8 Mice

As populations increase their life expectancy, age-related neurodegenerative disorders such as Alzheimer’s disease have become more common. I 2 -Imidazoline receptors (I 2 -IR) are widely distributed in the central nervous system, and dysregulation of I 2 -IR in patients with neurodegenerative disea...

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Published in:Neurotherapeutics 2019-04, Vol.16 (2), p.416-431
Main Authors: Griñán-Ferré, Christian, Vasilopoulou, Foteini, Abás, Sònia, Rodríguez-Arévalo, Sergio, Bagán, Andrea, Sureda, Francesc X., Pérez, Belén, Callado, Luis F., García-Sevilla, Jesús A., García-Fuster, M. Julia, Escolano, Carmen, Pallàs, Mercè
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Language:English
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Summary:As populations increase their life expectancy, age-related neurodegenerative disorders such as Alzheimer’s disease have become more common. I 2 -Imidazoline receptors (I 2 -IR) are widely distributed in the central nervous system, and dysregulation of I 2 -IR in patients with neurodegenerative diseases has been reported, suggesting their implication in cognitive impairment. This evidence indicates that high-affinity selective I 2 -IR ligands potentially contribute to the delay of neurodegeneration. In vivo studies in the female senescence accelerated mouse-prone 8 mice have shown that treatment with I 2 -IR ligands, MCR5 and MCR9 , produce beneficial effects in behavior and cognition. Changes in molecular pathways implicated in oxidative stress, inflammation, synaptic plasticity, and apoptotic cell death were also studied. Furthermore, treatments with these I 2 -IR ligands diminished the amyloid precursor protein processing pathway and increased Aβ degrading enzymes in the hippocampus of SAMP8 mice. These results collectively demonstrate the neuroprotective role of these new I 2 -IR ligands in a mouse model of brain aging through specific pathways and suggest their potential as therapeutic agents in brain disorders and age-related neurodegenerative diseases.
ISSN:1933-7213
1878-7479
1878-7479
DOI:10.1007/s13311-018-00681-5