Scientific Aged Brains Express Less Melanocortin Receptors, Which Correlates with Age-Related Decline of Cognitive Functions


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Aged Brains Express Less Melanocortin Receptors, Which Correlates with Age-Related Decline of Cognitive Functions

Published: 16 October 2021

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.
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@sharelooker Once again, what a valuable find!

"Within the hippocampus region, the MC4R has been the focus of study, especially in the context of AD. The MC4R was shown to regulate hippocampal synaptic plasticity in healthy mice as well as in an AD mouse model, through the cAMP-PKA signaling pathway [28,40]. Further studies demonstrated that MC4R activation protects against the disease progression in different AD mouse models [29,30,31,41]. In this study, we demonstrated that the MC4R might play a less important role in the context of normative aging. The MC4R expression level is not significantly different between young and aged rats, and no correlation was observed between the MC4R expression level and the performance of rats in spatial learning and memory. Instead, the MC1R and the MC3R, which have higher expression levels in the hippocampus than the MC4R and showed statistically significant correlations with the performance of aged rats in spatial learning and memory, may be better drug targets for the aging-related cognitive decline. Correlations between MC1R expression levels and cognitive decline during aging might be due to MC1R’s expression in glial cells and its ability to attenuate neuroinflammation through the Gs-cAMP-PKA pathway [42,43], as chronic inflammation has been proposed to be an important mechanism underlying cognitive decline and dementia [44]. ."

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