Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder
Abstract Introduction Repeated exposure to high doses of alcohol triggers neuroinflammatory processes that contribute to craving and mood dysfunction in alcohol use disorder (AUD). The upregulation of the translocator protein (TSPO) is considered a biomarker of neuroinflammation, and TSPO ligands ha...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-02-01
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| Series: | Brain and Behavior |
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| Online Access: | https://doi.org/10.1002/brb3.1961 |
| _version_ | 1819049834611474432 |
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| author | Luana Martins De Carvalho Corinde E. Wiers Hui Sun Gene‐Jack Wang Nora D. Volkow |
| author_facet | Luana Martins De Carvalho Corinde E. Wiers Hui Sun Gene‐Jack Wang Nora D. Volkow |
| author_sort | Luana Martins De Carvalho |
| collection | DOAJ |
| description | Abstract Introduction Repeated exposure to high doses of alcohol triggers neuroinflammatory processes that contribute to craving and mood dysfunction in alcohol use disorder (AUD). The upregulation of the translocator protein (TSPO) is considered a biomarker of neuroinflammation, and TSPO ligands have been used as neuroimaging biomarkers of neuroinflammation. Epigenetic mechanisms are also implicated in neuroinflammatory responses to alcohol, and elevated expression of HDAC2 and HDAC6 has been reported in the brain of animals exposed to chronic alcohol. Methods The present study examined the transcriptional regulation of TSPO, HDAC2, and HDAC6 in human postmortem brain tissue from males previously diagnosed with AUD (n = 11) compared to age‐matched nondependent males (n = 13) in four brain regions relevant to AUD: prefrontal cortex (PFC), nucleus accumbens (NAc), hippocampus (HPP), and amygdala (AMY). Results Translocator protein mRNA levels in AMY and PFC and HDAC2 and HDAC6 mRNA levels in AMY were upregulated in AUD compared to controls. In AMY, TSPO mRNA levels were positively associated with HDAC2 and HDAC6 mRNA levels, suggesting a possible regulation of TSPO by HDAC2 and HDAC6 in this brain region. In contrast, there were no group differences for TSPO, HDAC2, and HDAC6 in NAc and HPP. Conclusion Our study is the first to find upregulated TSPO mRNA levels in AMY and PFC in postmortem brains from AUD consistent with neuroinflammation, and in the amygdala, they implicate epigenetic regulation of TSPO by HDAC2 and HDAC6. |
| first_indexed | 2024-12-21T11:38:27Z |
| format | Article |
| id | doaj.art-856c91aca6184685a94355c3cbf5fca2 |
| institution | Directory Open Access Journal |
| issn | 2162-3279 |
| language | English |
| last_indexed | 2024-12-21T11:38:27Z |
| publishDate | 2021-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Brain and Behavior |
| spelling | doaj.art-856c91aca6184685a94355c3cbf5fca22022-12-21T19:05:22ZengWileyBrain and Behavior2162-32792021-02-01112n/an/a10.1002/brb3.1961Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorderLuana Martins De Carvalho0Corinde E. Wiers1Hui Sun2Gene‐Jack Wang3Nora D. Volkow4National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda MD USANational Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda MD USANational Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda MD USANational Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda MD USANational Institute on Alcohol Abuse and Alcoholism National Institutes of Health Bethesda MD USAAbstract Introduction Repeated exposure to high doses of alcohol triggers neuroinflammatory processes that contribute to craving and mood dysfunction in alcohol use disorder (AUD). The upregulation of the translocator protein (TSPO) is considered a biomarker of neuroinflammation, and TSPO ligands have been used as neuroimaging biomarkers of neuroinflammation. Epigenetic mechanisms are also implicated in neuroinflammatory responses to alcohol, and elevated expression of HDAC2 and HDAC6 has been reported in the brain of animals exposed to chronic alcohol. Methods The present study examined the transcriptional regulation of TSPO, HDAC2, and HDAC6 in human postmortem brain tissue from males previously diagnosed with AUD (n = 11) compared to age‐matched nondependent males (n = 13) in four brain regions relevant to AUD: prefrontal cortex (PFC), nucleus accumbens (NAc), hippocampus (HPP), and amygdala (AMY). Results Translocator protein mRNA levels in AMY and PFC and HDAC2 and HDAC6 mRNA levels in AMY were upregulated in AUD compared to controls. In AMY, TSPO mRNA levels were positively associated with HDAC2 and HDAC6 mRNA levels, suggesting a possible regulation of TSPO by HDAC2 and HDAC6 in this brain region. In contrast, there were no group differences for TSPO, HDAC2, and HDAC6 in NAc and HPP. Conclusion Our study is the first to find upregulated TSPO mRNA levels in AMY and PFC in postmortem brains from AUD consistent with neuroinflammation, and in the amygdala, they implicate epigenetic regulation of TSPO by HDAC2 and HDAC6.https://doi.org/10.1002/brb3.1961alcoholepigeneticsneuroinflammationTSPO |
| spellingShingle | Luana Martins De Carvalho Corinde E. Wiers Hui Sun Gene‐Jack Wang Nora D. Volkow Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder Brain and Behavior alcohol epigenetics neuroinflammation TSPO |
| title | Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder |
| title_full | Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder |
| title_fullStr | Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder |
| title_full_unstemmed | Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder |
| title_short | Increased transcription of TSPO, HDAC2, and HDAC6 in the amygdala of males with alcohol use disorder |
| title_sort | increased transcription of tspo hdac2 and hdac6 in the amygdala of males with alcohol use disorder |
| topic | alcohol epigenetics neuroinflammation TSPO |
| url | https://doi.org/10.1002/brb3.1961 |
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