Ginsenoside Re Protects against Serotonergic Behaviors Evoked by 2,5-Dimethoxy-4-iodo-amphetamine in Mice via Inhibition of PKCδ-Mediated Mitochondrial Dysfunction
It has been recognized that serotonin 2A receptor (5-HT2A) agonist 2,5-dimethoxy-4-iodo-amphetamine (DOI) impairs serotonergic homeostasis. However, the mechanism of DOI-induced serotonergic behaviors remains to be explored. Moreover, little is known about therapeutic interventions against serotonin syndrome, although evidence suggests that ginseng might possess modulating effects on the serotonin system. As ginsenoside Re (GRe) is well-known as a novel antioxidant in the nervous system, we investigated whether GRe modulates 5-HT2A receptor agonist DOI-induced serotonin impairments. We proposed that protein kinase Cδ (PKCδ) mediates serotonergic impairments. Treatment with GRe or 5-HT2A receptor antagonist MDL11939 significantly attenuated DOI-induced serotonergic behaviors (i.e., overall serotonergic syndrome behaviors, head twitch response, hyperthermia) by inhibiting mitochondrial translocation of PKCδ, reducing mitochondrial glutathione peroxidase activity, mitochondrial dysfunction, and mitochondrial oxidative stress in wild-type mice. These attenuations were in line with those observed upon PKCδ inhibition (i.e., pharmacologic inhibitor rottlerin or PKCδ knockout mice). Furthermore, GRe was not further implicated in attenuation mediated by PKCδ knockout in mice. Our results suggest that PKCδ is a therapeutic target for GRe against serotonergic behaviors induced by DOI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
International journal of molecular sciences - 22(2021), 13 vom: 05. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shin, Eun-Joo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.07.2021 Date Revised 26.07.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms22137219 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM328265772 |
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| 100 | 1 | |a Shin, Eun-Joo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ginsenoside Re Protects against Serotonergic Behaviors Evoked by 2,5-Dimethoxy-4-iodo-amphetamine in Mice via Inhibition of PKCδ-Mediated Mitochondrial Dysfunction |
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| 500 | |a Date Revised 26.07.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a It has been recognized that serotonin 2A receptor (5-HT2A) agonist 2,5-dimethoxy-4-iodo-amphetamine (DOI) impairs serotonergic homeostasis. However, the mechanism of DOI-induced serotonergic behaviors remains to be explored. Moreover, little is known about therapeutic interventions against serotonin syndrome, although evidence suggests that ginseng might possess modulating effects on the serotonin system. As ginsenoside Re (GRe) is well-known as a novel antioxidant in the nervous system, we investigated whether GRe modulates 5-HT2A receptor agonist DOI-induced serotonin impairments. We proposed that protein kinase Cδ (PKCδ) mediates serotonergic impairments. Treatment with GRe or 5-HT2A receptor antagonist MDL11939 significantly attenuated DOI-induced serotonergic behaviors (i.e., overall serotonergic syndrome behaviors, head twitch response, hyperthermia) by inhibiting mitochondrial translocation of PKCδ, reducing mitochondrial glutathione peroxidase activity, mitochondrial dysfunction, and mitochondrial oxidative stress in wild-type mice. These attenuations were in line with those observed upon PKCδ inhibition (i.e., pharmacologic inhibitor rottlerin or PKCδ knockout mice). Furthermore, GRe was not further implicated in attenuation mediated by PKCδ knockout in mice. Our results suggest that PKCδ is a therapeutic target for GRe against serotonergic behaviors induced by DOI | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a PKCδ knockout mice | |
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| 650 | 4 | |a hyperthermia | |
| 650 | 4 | |a hypothalamus | |
| 650 | 4 | |a mitochondrial burden | |
| 650 | 4 | |a serotonergic behaviors | |
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| 700 | 1 | |a Jeong, Ji Hoon |e verfasserin |4 aut | |
| 700 | 1 | |a Nguyen, Bao-Trong |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Naveen |e verfasserin |4 aut | |
| 700 | 1 | |a Nah, Seung-Yeol |e verfasserin |4 aut | |
| 700 | 1 | |a Chung, Yoon Hee |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Byun, Jae Kyung |e verfasserin |4 aut | |
| 700 | 1 | |a Nabeshima, Toshitaka |e verfasserin |4 aut | |
| 700 | 1 | |a Ko, Sung Kwon |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Hyoung-Chun |e verfasserin |4 aut | |
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