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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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3407212?pdf=render |
| _version_ | 1818585609239789568 |
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| author | Hong Sun Wanfen Xiong Denise M Arrick William G Mayhan |
| author_facet | Hong Sun Wanfen Xiong Denise M Arrick William G Mayhan |
| author_sort | Hong Sun |
| collection | DOAJ |
| 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. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:39:47Z |
| publishDate | 2012-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-283f17d8906340109174aeb521d42b3d2022-12-21T22:37:43ZengPublic 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 |
| 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 |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC3407212?pdf=render |
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