Behavioral and Cognitive Improvement Induced by Novel Imidazoline I 2 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 -Imidazoline receptors (I -IR) are widely distributed in the central nervous system, and dysregulation of I -IR in patients with neurodegenerative diseas...

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Bibliographic Details
Published in:Neurotherapeutics 2019-04, Vol.16 (2), p.416
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
Format: Article
Language:English
Subjects:
Aging - drug effects
Aging - metabolism
Amyloid beta-Protein Precursor - metabolism
Animals
Apoptosis - drug effects
Behavior, Animal - drug effects
Cognition - drug effects
Disease Models, Animal
Female
Hippocampus - drug effects
Hippocampus - metabolism
Imidazoline Receptors - agonists
Mice
Oxidative Stress - drug effects
Recognition, Psychology - drug effects
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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 -Imidazoline receptors (I -IR) are widely distributed in the central nervous system, and dysregulation of I -IR in patients with neurodegenerative diseases has been reported, suggesting their implication in cognitive impairment. This evidence indicates that high-affinity selective I -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 -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 -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 -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:1878-7479
DOI:10.1007/s13311-018-00681-5