AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models
Abstract Major depressive disorder (MDD) is a highly heterogeneous psychiatric disorder. The pathogenesis of MDD remained unclear, and it may be associated with exposure to different stressors. Most previous studies have focused on molecular changes in a single stress-induced depression model, which...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-06-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02486-3 |
| _version_ | 1797801244637528064 |
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| author | Xuemei Li Teng Teng Wei Yan Li Fan Xueer Liu Gerard Clarke Dan Zhu Yuanliang Jiang Yajie Xiang Ying Yu Yuqing Zhang Bangmin Yin Lin Lu Xinyu Zhou Peng Xie |
| author_facet | Xuemei Li Teng Teng Wei Yan Li Fan Xueer Liu Gerard Clarke Dan Zhu Yuanliang Jiang Yajie Xiang Ying Yu Yuqing Zhang Bangmin Yin Lin Lu Xinyu Zhou Peng Xie |
| author_sort | Xuemei Li |
| collection | DOAJ |
| description | Abstract Major depressive disorder (MDD) is a highly heterogeneous psychiatric disorder. The pathogenesis of MDD remained unclear, and it may be associated with exposure to different stressors. Most previous studies have focused on molecular changes in a single stress-induced depression model, which limited the identification of the pathogenesis of MDD. The depressive-like behaviors were induced by four well-validated stress models in rats, including chronic unpredictable mild stress, learned helplessness stress, chronic restraint stress and social defeat stress. We applied proteomic and metabolomic to investigate molecular changes in the hippocampus of those four models and revealed 529 proteins and 98 metabolites. Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified differentially regulated canonical pathways, and then we presented a schematic model that simulates AKT and MAPK signaling pathways network and their interactions and revealed the cascade reactions. Further, the western blot confirmed that p-AKT, p-ERK12, GluA1, p-MEK1, p-MEK2, p-P38, Syn1, and TrkB, which were changed in at least one depression model. Importantly, p-AKT, p-ERK12, p-MEK1 and p-P38 were identified as common alterations in four depression models. The molecular level changes caused by different stressors may be dramatically different, and even opposite, between four depression models. However, the different molecular alterations converge on a common AKT and MAPK molecular pathway. Further studies of these pathways could contribute to a better understanding of the pathogenesis of depression, with the ultimate goal of helping to develop or select more effective treatment strategies for MDD. |
| first_indexed | 2024-03-13T04:47:30Z |
| format | Article |
| id | doaj.art-77adb03a0c504230acaf01d97d39f810 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-13T04:47:30Z |
| publishDate | 2023-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-77adb03a0c504230acaf01d97d39f8102023-06-18T11:25:30ZengNature Publishing GroupTranslational Psychiatry2158-31882023-06-0113111010.1038/s41398-023-02486-3AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced modelsXuemei Li0Teng Teng1Wei Yan2Li Fan3Xueer Liu4Gerard Clarke5Dan Zhu6Yuanliang Jiang7Yajie Xiang8Ying Yu9Yuqing Zhang10Bangmin Yin11Lin Lu12Xinyu Zhou13Peng Xie14Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Psychiatry, The First Affiliated Hospital of Chongqing Medical UniversityPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Psychiatry and Neurobehavioural Science, University College CorkDepartment of Neurology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Psychiatry, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Psychiatry, The First Affiliated Hospital of Chongqing Medical UniversityPeking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical UniversityNHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Major depressive disorder (MDD) is a highly heterogeneous psychiatric disorder. The pathogenesis of MDD remained unclear, and it may be associated with exposure to different stressors. Most previous studies have focused on molecular changes in a single stress-induced depression model, which limited the identification of the pathogenesis of MDD. The depressive-like behaviors were induced by four well-validated stress models in rats, including chronic unpredictable mild stress, learned helplessness stress, chronic restraint stress and social defeat stress. We applied proteomic and metabolomic to investigate molecular changes in the hippocampus of those four models and revealed 529 proteins and 98 metabolites. Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified differentially regulated canonical pathways, and then we presented a schematic model that simulates AKT and MAPK signaling pathways network and their interactions and revealed the cascade reactions. Further, the western blot confirmed that p-AKT, p-ERK12, GluA1, p-MEK1, p-MEK2, p-P38, Syn1, and TrkB, which were changed in at least one depression model. Importantly, p-AKT, p-ERK12, p-MEK1 and p-P38 were identified as common alterations in four depression models. The molecular level changes caused by different stressors may be dramatically different, and even opposite, between four depression models. However, the different molecular alterations converge on a common AKT and MAPK molecular pathway. Further studies of these pathways could contribute to a better understanding of the pathogenesis of depression, with the ultimate goal of helping to develop or select more effective treatment strategies for MDD.https://doi.org/10.1038/s41398-023-02486-3 |
| spellingShingle | Xuemei Li Teng Teng Wei Yan Li Fan Xueer Liu Gerard Clarke Dan Zhu Yuanliang Jiang Yajie Xiang Ying Yu Yuqing Zhang Bangmin Yin Lin Lu Xinyu Zhou Peng Xie AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models Translational Psychiatry |
| title | AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models |
| title_full | AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models |
| title_fullStr | AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models |
| title_full_unstemmed | AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models |
| title_short | AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models |
| title_sort | akt and mapk signaling pathways in hippocampus reveals the pathogenesis of depression in four stress induced models |
| url | https://doi.org/10.1038/s41398-023-02486-3 |
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