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Activation of melanocortin-4 receptor by a synthetic agonist inhibits ethanolinduced neuroinflammation in rats

dc.contributor.authorFlores-Bastías O.
dc.contributor.authorGómez G.I.
dc.contributor.authorOrellana J.A.
dc.contributor.authorKarahanian E.
dc.date.accessioned2020-09-02T22:17:53Z
dc.date.available2020-09-02T22:17:53Z
dc.date.issued2019
dc.identifier10.2174/1381612825666191216145153
dc.identifier.citation25, 45, 4799-4805
dc.identifier.issn13816128
dc.identifier.urihttps://hdl.handle.net/20.500.12728/4486
dc.descriptionBackground: High ethanol intake induces a neuroinflammatory response resulting in the subsequent maintenance of chronic alcohol consumption. The melanocortin system plays a pivotal role in the modulation of alcohol consumption. Interestingly, it has been shown that the activation of melanocortin-4 receptor (MC4R) in the brain decreases the neuroinflammatory response in models of brain damage other than alcohol consumption, such as LPS-induced neuroinflammation, cerebral ischemia, glutamate excitotoxicity, and spinal cord injury.Objectives: In this work, we aimed to study whether MC4R activation by a synthetic MC4R-agonist peptide prevents ethanol-induced neuroinflammation, and if alcohol consumption produces changes in MC4R expression in the hippocampus and hypothalamus.Methods: Ethanol-preferring Sprague Dawley rats were selected offering access to 20% ethanol on alternate days for 4 weeks (intermittent access protocol). After this time, animals were i.p. administered an MC4R agonist peptide in the last 2 days of the protocol. Then, the expression of the proinflammatory cytokines interleukin 6 (IL-6), interleukin 1-beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured in the hippocampus, hypothalamus and prefrontal cortex. It was also evaluated if ethanol intake produces alterations in the expression of MC4R in the hippocampus and the hypothalamus.Results: Alcohol consumption increased the expression of MC4R in the hippocampus and the hypothalamus. The administration of the MC4R agonist reduced IL-6, IL-1β and TNF-α levels in hippocampus, hypothalamus and prefrontal cortex, to those observed in control rats that did not drink alcohol.Conclusion: High ethanol consumption produces an increase in the expression of MC4R in the hippocampus and hypothalamus. The administration of a synthetic MC4R-agonist peptide prevents neuroinflammation induced by alcohol consumption in the hippocampus, hypothalamus, and prefrontal cortex. These results could explain the effect of α-MSH and other synthetic MC4R agonists in decreasing alcohol intake through the reduction of the ethanol-induced inflammatory response in the brain. © 2019 Bentham Science Publishers.
dc.language.isoen
dc.publisherBentham Science Publishers
dc.subjectAlcohol use disorder
dc.subjectHypothalamus
dc.subjectMC4R
dc.subjectMelanocortin
dc.subjectNeuroinflammation
dc.subjectα-MSH
dc.subjectalpha intermedin
dc.subjectcyclo(beta alanylhistidyl dextro phenylalanylarginyltryptophanylglutamic acid)amide
dc.subjectinterleukin 1beta
dc.subjectinterleukin 6
dc.subjectmelanocortin 4 receptor
dc.subjectmelanocortin receptor agonist
dc.subjecttumor necrosis factor
dc.subjectunclassified drug
dc.subjectalcohol
dc.subjectalpha intermedin
dc.subjectmelanocortin 4 receptor
dc.subjectmelanocortin receptor type 4, rat
dc.subjectalcohol consumption
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectantiinflammatory activity
dc.subjectArticle
dc.subjectcontrolled study
dc.subjecthippocampus
dc.subjecthormonal regulation
dc.subjecthypothalamus
dc.subjectmale
dc.subjectnervous system inflammation
dc.subjectnonhuman
dc.subjectprefrontal cortex
dc.subjectpriority journal
dc.subjectprotein expression
dc.subjectprotein expression level
dc.subjectrat
dc.subjectSprague Dawley rat
dc.subjectanimal
dc.subjectdrug effect
dc.subjectinflammation
dc.subjectalpha-MSH
dc.subjectAnimals
dc.subjectEthanol
dc.subjectHippocampus
dc.subjectHypothalamus
dc.subjectInflammation
dc.subjectPrefrontal Cortex
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectReceptor, Melanocortin, Type 4
dc.titleActivation of melanocortin-4 receptor by a synthetic agonist inhibits ethanolinduced neuroinflammation in rats
dc.typeArticle


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