Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ.
We examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption.C57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8 weeks, orally treated...
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doaj-283f17d8906340109174aeb521d42b3d2020-11-25T01:24:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4171610.1371/journal.pone.0041716Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ.Hong SunWanfen XiongDenise M ArrickWilliam G MayhanWe examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption.C57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8 weeks, orally treated with rosiglitazone (20 mg/kg/day), a peroxisome proliferator-activated receptor gamma (PPARγ)-selective agonist, or GW9662 (3 mg/kg/day), a selective PPARγ antagonist, for 2 weeks. The mice were subjected to unilateral middle cerebral artery occlusion (MCAO) for 90 minutes. Brain injury, DNA fragmentation and nuclear PPARγ protein/activity were evaluated at 24 hours of reperfusion. We found that the brain injury and DNA fragmentation were reduced in 1% alcohol-fed mice compared to nonalcohol-fed mice. Rosiglitazone suppressed the brain injury in nonalcohol-fed mice, but didn't alter the brain injury in alcohol-fed mice. In contrast, GW9662 worsened the brain injury in alcohol-fed mice, but didn't alter the brain injury in nonalcohol-fed mice. Nuclear PPARγ protein/activity at peri-infarct and the contralateral corresponding areas of the parietal cortex was greater in alcohol-fed mice compared to nonalcohol-fed mice. Using differentiated catecholaminergic (CATH.a) neurons, we measured dose-related influences of chronic alcohol exposure on nuclear PPARγ protein/activity and the influence of low-dose alcohol exposure on 2-hour oxygen-glucose deprivation (OGD)/24-hour reoxygenation-induced apoptosis. We found that low-dose alcohol exposure increased nuclear PPARγ protein/activity and protected against the OGD/reoxygenation-induced apoptosis. The beneficial effect of low-dose alcohol exposure on OGD/reoxygenation-induced apoptosis was abolished by GW9662.Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury. The neuroprotective effect of low-dose alcohol consumption may be related to an upregulated PPARγ.http://europepmc.org/articles/PMC3407212?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hong Sun Wanfen Xiong Denise M Arrick William G Mayhan |
spellingShingle |
Hong Sun Wanfen Xiong Denise M Arrick William G Mayhan Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ. PLoS ONE |
author_facet |
Hong Sun Wanfen Xiong Denise M Arrick William G Mayhan |
author_sort |
Hong Sun |
title |
Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ. |
title_short |
Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ. |
title_full |
Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ. |
title_fullStr |
Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ. |
title_full_unstemmed |
Low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of PPARγ. |
title_sort |
low-dose alcohol consumption protects against transient focal cerebral ischemia in mice: possible role of pparγ. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
We examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption.C57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8 weeks, orally treated with rosiglitazone (20 mg/kg/day), a peroxisome proliferator-activated receptor gamma (PPARγ)-selective agonist, or GW9662 (3 mg/kg/day), a selective PPARγ antagonist, for 2 weeks. The mice were subjected to unilateral middle cerebral artery occlusion (MCAO) for 90 minutes. Brain injury, DNA fragmentation and nuclear PPARγ protein/activity were evaluated at 24 hours of reperfusion. We found that the brain injury and DNA fragmentation were reduced in 1% alcohol-fed mice compared to nonalcohol-fed mice. Rosiglitazone suppressed the brain injury in nonalcohol-fed mice, but didn't alter the brain injury in alcohol-fed mice. In contrast, GW9662 worsened the brain injury in alcohol-fed mice, but didn't alter the brain injury in nonalcohol-fed mice. Nuclear PPARγ protein/activity at peri-infarct and the contralateral corresponding areas of the parietal cortex was greater in alcohol-fed mice compared to nonalcohol-fed mice. Using differentiated catecholaminergic (CATH.a) neurons, we measured dose-related influences of chronic alcohol exposure on nuclear PPARγ protein/activity and the influence of low-dose alcohol exposure on 2-hour oxygen-glucose deprivation (OGD)/24-hour reoxygenation-induced apoptosis. We found that low-dose alcohol exposure increased nuclear PPARγ protein/activity and protected against the OGD/reoxygenation-induced apoptosis. The beneficial effect of low-dose alcohol exposure on OGD/reoxygenation-induced apoptosis was abolished by GW9662.Our findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury. The neuroprotective effect of low-dose alcohol consumption may be related to an upregulated PPARγ. |
url |
http://europepmc.org/articles/PMC3407212?pdf=render |
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