Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats
Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00535/full |
| _version_ | 1818341873997053952 |
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| author | Peifang Liu Hui Li Yueqiu Wang Xiaolin Su Yang Li Meiling Yan Lan Ma Hui Che |
| author_facet | Peifang Liu Hui Li Yueqiu Wang Xiaolin Su Yang Li Meiling Yan Lan Ma Hui Che |
| author_sort | Peifang Liu |
| collection | DOAJ |
| description | Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction. |
| first_indexed | 2024-12-13T16:05:43Z |
| format | Article |
| id | doaj.art-6a59a3fd7c3841bfb5807d004f92ef67 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T16:05:43Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6a59a3fd7c3841bfb5807d004f92ef672022-12-21T23:39:03ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-05-011110.3389/fphar.2020.00535522438Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic RatsPeifang Liu0Hui Li1Yueqiu Wang2Xiaolin Su3Yang Li4Meiling Yan5Lan Ma6Hui Che7Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United StatesDepartment of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaThe Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou, ChinaDepartment of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, ChinaDiabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction.https://www.frontiersin.org/article/10.3389/fphar.2020.00535/fullharminediabetes mellituscognitive dysfunctionNLRP3 inflammasomeBDNF |
| spellingShingle | Peifang Liu Hui Li Yueqiu Wang Xiaolin Su Yang Li Meiling Yan Lan Ma Hui Che Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats Frontiers in Pharmacology harmine diabetes mellitus cognitive dysfunction NLRP3 inflammasome BDNF |
| title | Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats |
| title_full | Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats |
| title_fullStr | Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats |
| title_full_unstemmed | Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats |
| title_short | Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats |
| title_sort | harmine ameliorates cognitive impairment by inhibiting nlrp3 inflammasome activation and enhancing the bdnf trkb signaling pathway in stz induced diabetic rats |
| topic | harmine diabetes mellitus cognitive dysfunction NLRP3 inflammasome BDNF |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00535/full |
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