The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice
Abstract Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-11-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02647-4 |
| _version_ | 1797556257714864128 |
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| author | Rui Chang Shanshan Zhu Jionghong Peng Zhenyi Lang Xinyu Zhou Hailin Liao Ju Zou Peng Zeng Sijie Tan |
| author_facet | Rui Chang Shanshan Zhu Jionghong Peng Zhenyi Lang Xinyu Zhou Hailin Liao Ju Zou Peng Zeng Sijie Tan |
| author_sort | Rui Chang |
| collection | DOAJ |
| description | Abstract Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the treatment of several psychiatric diseases, such as drug addiction and post-traumatic stress disorder. Fat mass and obesity-associated gene (FTO) is a novel demethylase of N6-methyladenosine (m6A) and it has been intensively involved in learning and memory. However, the role of FTO in memory reconsolidation has not been determined. In the present study, the function of FTO in memory reconsolidation was investigated in the novel object recognition (NOR) model in mice. The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. MA downregulated BDNF expression during NOR memory reconsolidation in the hippocampus, while the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) reversed the disruptive effects of MA on NOR memory reconsolidation. Furthermore, overexpression of FTO increased BDNF expression via decreasing mRNA m6A in HT22 cells. Taken together, these results indicate that FTO may up-regulate the BDNF-TrkB pathway to promote NOR memory reconsolidation through m6A modification. |
| first_indexed | 2024-03-10T17:00:16Z |
| format | Article |
| id | doaj.art-c9f32e7e60944538ac15098d9b9dd49e |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-10T17:00:16Z |
| publishDate | 2023-11-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-c9f32e7e60944538ac15098d9b9dd49e2023-11-20T11:00:28ZengNature Publishing GroupTranslational Psychiatry2158-31882023-11-011311810.1038/s41398-023-02647-4The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in miceRui Chang0Shanshan Zhu1Jionghong Peng2Zhenyi Lang3Xinyu Zhou4Hailin Liao5Ju Zou6Peng Zeng7Sijie Tan8Department of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaDepartment of Histology and Embryology, School of Basic Medicine, Hengyang Medical School, University of South ChinaAbstract Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the treatment of several psychiatric diseases, such as drug addiction and post-traumatic stress disorder. Fat mass and obesity-associated gene (FTO) is a novel demethylase of N6-methyladenosine (m6A) and it has been intensively involved in learning and memory. However, the role of FTO in memory reconsolidation has not been determined. In the present study, the function of FTO in memory reconsolidation was investigated in the novel object recognition (NOR) model in mice. The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. MA downregulated BDNF expression during NOR memory reconsolidation in the hippocampus, while the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) reversed the disruptive effects of MA on NOR memory reconsolidation. Furthermore, overexpression of FTO increased BDNF expression via decreasing mRNA m6A in HT22 cells. Taken together, these results indicate that FTO may up-regulate the BDNF-TrkB pathway to promote NOR memory reconsolidation through m6A modification.https://doi.org/10.1038/s41398-023-02647-4 |
| spellingShingle | Rui Chang Shanshan Zhu Jionghong Peng Zhenyi Lang Xinyu Zhou Hailin Liao Ju Zou Peng Zeng Sijie Tan The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice Translational Psychiatry |
| title | The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice |
| title_full | The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice |
| title_fullStr | The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice |
| title_full_unstemmed | The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice |
| title_short | The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice |
| title_sort | hippocampal fto bdnf trkb pathway is required for novel object recognition memory reconsolidation in mice |
| url | https://doi.org/10.1038/s41398-023-02647-4 |
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