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

• Published in: Neurotherapeutics Vol. 16; no. 2; pp. 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
• Format: Journal Article
• Language: English
• Published: Cham Elsevier Inc 01.04.2019; Springer International Publishing; Springer Nature B.V; Springer Verlag
• Subjects: (2-imidazolin-4-yl)phosphonates; Aging; Alzheimer's disease; Amyloid precursor protein; Apoptosis; Behavior; Behavioral plasticity; Biomedical and Life Sciences; Biomedicine; Cell death; Central nervous system; Cognition; Cognitive ability; Envelliment; Imidazoline; Imidazoline I2 receptors; Imidazoline receptors; Life span; Ligands; Malaltia d'Alzheimer; Malalties neurodegeneratives; Neurobiology; Neurodegeneration; Neurodegenerative Diseases; Neurology; Neuroprotection; Neurosciences; Neurosurgery; Original; Original Article; Oxidative stress; Senescence; Synaptic plasticity; Neuroprotection; Neurodegeneration; Aging; Cognition; Behavior; Imidazoline I2 receptors; (2-imidazolin-4-yl)phosphonates; Imidazoline I; receptors
• ISSN: 1878-7479; 1933-7213; 1878-7479
• DOI: 10.1007/s13311-018-00681-5

As populations increase their life expectancy, age-related neurodegenerative disorders such as Alzheimer's disease have become more common. I2-Imidazoline receptors (I2-IR) are widely distributed in the central nervous system, and dysregulation of I2-IR in patients with neurodegenerative diseases has been reported, suggesting their implication in cognitive impairment. This evidence indicates that high-affinity selective I2-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 I2-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 I2-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 I2-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.