Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF
Stress has been implicated in the etiology of neurological and psychological illnesses. Chronic social isolation (SI) is a psychological stressor that provokes neurobehavioral changes associated with psychiatric disorders, including anxiety disorders. Mitochondria dysfunction and oxidative stress ar...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289522000741 |
| _version_ | 1811300240085483520 |
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| author | Alzahra J. Al Omran Saki Watanabe Ethan C. Hong Samantha G. Skinner Mindy Zhang Jifeng Zhang Xuesi M. Shao Jing Liang |
| author_facet | Alzahra J. Al Omran Saki Watanabe Ethan C. Hong Samantha G. Skinner Mindy Zhang Jifeng Zhang Xuesi M. Shao Jing Liang |
| author_sort | Alzahra J. Al Omran |
| collection | DOAJ |
| description | Stress has been implicated in the etiology of neurological and psychological illnesses. Chronic social isolation (SI) is a psychological stressor that provokes neurobehavioral changes associated with psychiatric disorders, including anxiety disorders. Mitochondria dysfunction and oxidative stress are hallmarks of anxiety pathogenesis. Here we demonstrate the effects of SI-induced stress on mitochondrial function, antioxidative enzymes, autophagy, and brain derivative neurotrophic factor (BDNF). SI induced a reduction in electron transport chain subunits C–I, C-II, and C-VI and an increase in hydrogen peroxide. Treatment with dihydromyricetin (DHM), extracted from Ampelopsis grossedentata, counteracted these changes. A dramatic increase in several primary mitochondrial antioxidative enzymes such as superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), peroxiredoxin-3 (PRDX3), and glutathione peroxidase 4 (GPX4) was observed after SI and a repeated episode of SI. Both SI and repeated SI induced a reduction in sequestosome 1 (SQSTM1/p62). However, only repeated SI modulated autophagy primary protein beclin-1 (Bcl-1). In addition, SI and repeated SI modulated the BDNF-TrkB signaling pathway and the phosphorylation of the downstream extracellular signal-regulated MAP kinase1/2 (p-Erk p42 and p-Erk p44) cascade. DHM treatment ameliorated these changes. Collectively, we demonstrated that DHM treatment counteracted the effects of SI and repeated SI on antioxidative enzymes, autophagy, and the BDNF-TrkB signaling pathway. These findings highlight the molecular mechanisms that partially explain the anxiolytic effects of DHM. |
| first_indexed | 2024-04-13T06:48:13Z |
| format | Article |
| id | doaj.art-3ff5cb41b02c4e75a9414bf99aa3f4a7 |
| institution | Directory Open Access Journal |
| issn | 2352-2895 |
| language | English |
| last_indexed | 2024-04-13T06:48:13Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj.art-3ff5cb41b02c4e75a9414bf99aa3f4a72022-12-22T02:57:29ZengElsevierNeurobiology of Stress2352-28952022-11-0121100499Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNFAlzahra J. Al Omran0Saki Watanabe1Ethan C. Hong2Samantha G. Skinner3Mindy Zhang4Jifeng Zhang5Xuesi M. Shao6Jing Liang7Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, 90033, USATitus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, 90033, USATitus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, 90033, USATitus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, 90033, USATitus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, 90033, USATitus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, 90033, USANeurobiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, 90095, USATitus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA, 90033, USA; Corresponding author.Stress has been implicated in the etiology of neurological and psychological illnesses. Chronic social isolation (SI) is a psychological stressor that provokes neurobehavioral changes associated with psychiatric disorders, including anxiety disorders. Mitochondria dysfunction and oxidative stress are hallmarks of anxiety pathogenesis. Here we demonstrate the effects of SI-induced stress on mitochondrial function, antioxidative enzymes, autophagy, and brain derivative neurotrophic factor (BDNF). SI induced a reduction in electron transport chain subunits C–I, C-II, and C-VI and an increase in hydrogen peroxide. Treatment with dihydromyricetin (DHM), extracted from Ampelopsis grossedentata, counteracted these changes. A dramatic increase in several primary mitochondrial antioxidative enzymes such as superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), peroxiredoxin-3 (PRDX3), and glutathione peroxidase 4 (GPX4) was observed after SI and a repeated episode of SI. Both SI and repeated SI induced a reduction in sequestosome 1 (SQSTM1/p62). However, only repeated SI modulated autophagy primary protein beclin-1 (Bcl-1). In addition, SI and repeated SI modulated the BDNF-TrkB signaling pathway and the phosphorylation of the downstream extracellular signal-regulated MAP kinase1/2 (p-Erk p42 and p-Erk p44) cascade. DHM treatment ameliorated these changes. Collectively, we demonstrated that DHM treatment counteracted the effects of SI and repeated SI on antioxidative enzymes, autophagy, and the BDNF-TrkB signaling pathway. These findings highlight the molecular mechanisms that partially explain the anxiolytic effects of DHM.http://www.sciencedirect.com/science/article/pii/S2352289522000741StressAnxietyDihydromyricetin (DHM)MitochondriaAntioxidative enzymesOxidative stress |
| spellingShingle | Alzahra J. Al Omran Saki Watanabe Ethan C. Hong Samantha G. Skinner Mindy Zhang Jifeng Zhang Xuesi M. Shao Jing Liang Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF Neurobiology of Stress Stress Anxiety Dihydromyricetin (DHM) Mitochondria Antioxidative enzymes Oxidative stress |
| title | Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF |
| title_full | Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF |
| title_fullStr | Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF |
| title_full_unstemmed | Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF |
| title_short | Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF |
| title_sort | dihydromyricetin ameliorates social isolation induced anxiety by modulating mitochondrial function antioxidant enzymes and bdnf |
| topic | Stress Anxiety Dihydromyricetin (DHM) Mitochondria Antioxidative enzymes Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S2352289522000741 |
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