The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD
Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcy...
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2020-08-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/9/1982 |
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| author | HyunHee Park Kyung-Min Han Hyongjun Jeon Ji-Soo Lee Hyunju Lee Seong Gak Jeon Jin-Hee Park Yu Gyung Kim Yuxi Lin Young-Ho Lee Yun Ha Jeong Hyang-Sook Hoe |
| author_facet | HyunHee Park Kyung-Min Han Hyongjun Jeon Ji-Soo Lee Hyunju Lee Seong Gak Jeon Jin-Hee Park Yu Gyung Kim Yuxi Lin Young-Ho Lee Yun Ha Jeong Hyang-Sook Hoe |
| author_sort | HyunHee Park |
| collection | DOAJ |
| description | Monoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aβ-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aβ-induced neuroinflammatory responses in vitro and in vivo. |
| first_indexed | 2024-03-10T16:43:42Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T16:43:42Z |
| publishDate | 2020-08-01 |
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| series | Cells |
| spelling | doaj.art-3cf5c5dad4cc48398d29dfae6a5b18ef2023-11-20T11:45:56ZengMDPI AGCells2073-44092020-08-0199198210.3390/cells9091982The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of ADHyunHee Park0Kyung-Min Han1Hyongjun Jeon2Ji-Soo Lee3Hyunju Lee4Seong Gak Jeon5Jin-Hee Park6Yu Gyung Kim7Yuxi Lin8Young-Ho Lee9Yun Ha Jeong10Hyang-Sook Hoe11Department of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaResearch Center of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Ochang, Cheongju, Chungbuk 28119, KoreaResearch Center of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Ochang, Cheongju, Chungbuk 28119, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaDepartment of Neural Development and Disease, Korea Brain Research Institute (KBRI), 61, Cheomdan-ro, Dong-gu, Daegu 41062, KoreaMonoamine oxidase (MAO) has been implicated in neuroinflammation, and therapies targeting MAO are of interest for neurodegenerative diseases. The small-molecule drug tranylcypromine, an inhibitor of MAO, is currently used as an antidepressant and in the treatment of cancer. However, whether tranylcypromine can regulate LPS- and/or Aβ-induced neuroinflammation in the brain has not been well-studied. In the present study, we found that tranylcypromine selectively altered LPS-induced proinflammatory cytokine levels in BV2 microglial cells but not primary astrocytes. In addition, tranylcypromine modulated LPS-mediated TLR4/ERK/STAT3 signaling to alter neuroinflammatory responses in BV2 microglial cells. Importantly, tranylcypromine significantly reduced microglial activation as well as proinflammatory cytokine levels in LPS-injected wild-type mice. Moreover, injection of tranylcypromine in 5xFAD mice (a mouse model of AD) significantly decreased microglial activation but had smaller effects on astrocyte activation. Taken together, our results suggest that tranylcypromine can suppress LPS- and Aβ-induced neuroinflammatory responses in vitro and in vivo.https://www.mdpi.com/2073-4409/9/9/1982neuroinflammationMAO inhibitormicrogliaamyloid betaLPS |
| spellingShingle | HyunHee Park Kyung-Min Han Hyongjun Jeon Ji-Soo Lee Hyunju Lee Seong Gak Jeon Jin-Hee Park Yu Gyung Kim Yuxi Lin Young-Ho Lee Yun Ha Jeong Hyang-Sook Hoe The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD Cells neuroinflammation MAO inhibitor microglia amyloid beta LPS |
| title | The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD |
| title_full | The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD |
| title_fullStr | The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD |
| title_full_unstemmed | The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD |
| title_short | The MAO Inhibitor Tranylcypromine Alters LPS- and Aβ-Mediated Neuroinflammatory Responses in Wild-type Mice and a Mouse Model of AD |
| title_sort | mao inhibitor tranylcypromine alters lps and aβ mediated neuroinflammatory responses in wild type mice and a mouse model of ad |
| topic | neuroinflammation MAO inhibitor microglia amyloid beta LPS |
| url | https://www.mdpi.com/2073-4409/9/9/1982 |
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