Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity.
The prefrontal cortex (PFC) is a brain region responsible for executive functions including working memory, impulse control and decision making. The loss of these functions may ultimately lead to addiction. Using histological analysis combined with stereological technique, we demonstrated that the P...
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Public Library of Science (PLoS)
2014
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oai:doaj.org-article:883b4040c7ad4fad97004ab2b9caffee2021-11-25T06:01:52ZDifferential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity.1932-620310.1371/journal.pone.0106945https://doaj.org/article/883b4040c7ad4fad97004ab2b9caffee2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25188266/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The prefrontal cortex (PFC) is a brain region responsible for executive functions including working memory, impulse control and decision making. The loss of these functions may ultimately lead to addiction. Using histological analysis combined with stereological technique, we demonstrated that the PFC is more vulnerable to chronic alcohol-induced oxidative stress and neuronal cell death than the hippocampus. This increased vulnerability is evidenced by elevated oxidative stress-induced DNA damage and enhanced expression of apoptotic markers in PFC neurons. We also found that one-carbon metabolism (OCM) impairment plays a significant role in alcohol toxicity to the PFC seen from the difference in the effects of acute and chronic alcohol exposure on DNA repair and from exaggeration of the damaging effects upon additional OCM impairment in mice deficient in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR). Given that damage to the PFC leads to loss of executive function and addiction, our study may shed light on the mechanism of alcohol addiction.Anna-Kate FowlerJeremy ThompsonLixia ChenMarisela DagdaJanet DertienKatina Sylvestre S DossouRuin MoaddelSusan E BergesonInna I KrumanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 9, p e106945 (2014) |
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Medicine R Science Q |
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Medicine R Science Q Anna-Kate Fowler Jeremy Thompson Lixia Chen Marisela Dagda Janet Dertien Katina Sylvestre S Dossou Ruin Moaddel Susan E Bergeson Inna I Kruman Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. |
| description |
The prefrontal cortex (PFC) is a brain region responsible for executive functions including working memory, impulse control and decision making. The loss of these functions may ultimately lead to addiction. Using histological analysis combined with stereological technique, we demonstrated that the PFC is more vulnerable to chronic alcohol-induced oxidative stress and neuronal cell death than the hippocampus. This increased vulnerability is evidenced by elevated oxidative stress-induced DNA damage and enhanced expression of apoptotic markers in PFC neurons. We also found that one-carbon metabolism (OCM) impairment plays a significant role in alcohol toxicity to the PFC seen from the difference in the effects of acute and chronic alcohol exposure on DNA repair and from exaggeration of the damaging effects upon additional OCM impairment in mice deficient in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR). Given that damage to the PFC leads to loss of executive function and addiction, our study may shed light on the mechanism of alcohol addiction. |
| format |
article |
| author |
Anna-Kate Fowler Jeremy Thompson Lixia Chen Marisela Dagda Janet Dertien Katina Sylvestre S Dossou Ruin Moaddel Susan E Bergeson Inna I Kruman |
| author_facet |
Anna-Kate Fowler Jeremy Thompson Lixia Chen Marisela Dagda Janet Dertien Katina Sylvestre S Dossou Ruin Moaddel Susan E Bergeson Inna I Kruman |
| author_sort |
Anna-Kate Fowler |
| title |
Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. |
| title_short |
Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. |
| title_full |
Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. |
| title_fullStr |
Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. |
| title_full_unstemmed |
Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. |
| title_sort |
differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/883b4040c7ad4fad97004ab2b9caffee |
| work_keys_str_mv |
AT annakatefowler differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT jeremythompson differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT lixiachen differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT mariseladagda differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT janetdertien differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT katinasylvestresdossou differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT ruinmoaddel differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT susanebergeson differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity AT innaikruman differentialsensitivityofprefrontalcortexandhippocampustoalcoholinducedtoxicity |
| _version_ |
1718414293567799296 |