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Aged Brains Express Less Melanocortin Receptors,Which Correlates with Age-Related Decline of Cognitive Functions
Authors:Yang Zhou  Monica K Chawla  Jose L Rios-Monterrosa  Lingzhi Wang  Marc A Zempare  Victor J Hruby  Carol A Barnes  Minying Cai
Institution:1.Department of Chemistry & Biochemistry, The University of Arizona, Tucson, AZ 85721, USA; (Y.Z.); (J.L.R.-M.); (L.W.); (V.J.H.);2.Evelyn F. McKnight Brain Institute, The University of Arizona, Tucson, AZ 85721, USA; (M.K.C.); (M.A.Z.); (C.A.B.);3.Division of Neural Systems, Memory & Aging, The University of Arizona, Tucson, AZ 85721, USA;4.Department of Psychology, Neurology and Neuroscience, The University of Arizona, Tucson, AZ 85721, USA
Abstract:Brain G-protein coupled receptors have been hypothesized to be potential targets for maintaining or restoring cognitive function in normal aged individuals or in patients with neurodegenerative disease. A number of recent reports suggest that activation of melanocortin receptors (MCRs) in the brain can significantly improve cognitive functions of normal rodents and of different rodent models of the Alzheimer’s disease. However, the potential impact of normative aging on the expression of MCRs and their potential roles for modulating cognitive function remains to be elucidated. In the present study, we first investigated the expression of these receptors in six different brain regions of young (6 months) and aged (23 months) rats following assessment of their cognitive status. Correlation analysis was further performed to reveal potential contributions of MCR subtypes to spatial learning and memory. Our results revealed statistically significant correlations between the expression of several MCR subtypes in the frontal cortex/hypothalamus and the hippocampus regions and the rats’ performance in spatial learning and memory only in the aged rats. These findings support the hypothesis that aging has a direct impact on the expression and function of MCRs, establishing MCRs as potential drug targets to alleviate aging-induced decline of cognitive function.
Keywords:aging  melanocortin receptor  MC1R  MC3R  MC4R  MC5R  cognitive decline  hippocampus  frontal cortex
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