Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness
Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (prote...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2017/9160515 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832553498721386496 |
|---|---|
| author | Zhilu Zou Yin Chen Qinqin Shen Xiaoyan Guo Yuxuan Zhang Gang Chen |
| author_facet | Zhilu Zou Yin Chen Qinqin Shen Xiaoyan Guo Yuxuan Zhang Gang Chen |
| author_sort | Zhilu Zou |
| collection | DOAJ |
| description | Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling. |
| format | Article |
| id | doaj-art-c576aa96f0b046f1bbe03f35211fe54b |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-c576aa96f0b046f1bbe03f35211fe54b2025-02-03T05:53:54ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/91605159160515Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned HelplessnessZhilu Zou0Yin Chen1Qinqin Shen2Xiaoyan Guo3Yuxuan Zhang4Gang Chen5Center for Translational Systems Biology and Neuroscience and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaCenter for Translational Systems Biology and Neuroscience and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaCenter for Translational Systems Biology and Neuroscience and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaCenter for Translational Systems Biology and Neuroscience and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaCenter for Translational Systems Biology and Neuroscience and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaCenter for Translational Systems Biology and Neuroscience and Key Laboratory of Integrative Biomedicine for Brain Diseases, Nanjing University of Chinese Medicine, Nanjing 210023, ChinaYueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.http://dx.doi.org/10.1155/2017/9160515 |
| spellingShingle | Zhilu Zou Yin Chen Qinqin Shen Xiaoyan Guo Yuxuan Zhang Gang Chen Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness Neural Plasticity |
| title | Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness |
| title_full | Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness |
| title_fullStr | Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness |
| title_full_unstemmed | Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness |
| title_short | Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness |
| title_sort | neural plasticity associated with hippocampal pka creb and nmda signaling is involved in the antidepressant effect of repeated low dose of yueju pill on chronic mouse model of learned helplessness |
| url | http://dx.doi.org/10.1155/2017/9160515 |
| work_keys_str_mv | AT zhiluzou neuralplasticityassociatedwithhippocampalpkacrebandnmdasignalingisinvolvedintheantidepressanteffectofrepeatedlowdoseofyuejupillonchronicmousemodeloflearnedhelplessness AT yinchen neuralplasticityassociatedwithhippocampalpkacrebandnmdasignalingisinvolvedintheantidepressanteffectofrepeatedlowdoseofyuejupillonchronicmousemodeloflearnedhelplessness AT qinqinshen neuralplasticityassociatedwithhippocampalpkacrebandnmdasignalingisinvolvedintheantidepressanteffectofrepeatedlowdoseofyuejupillonchronicmousemodeloflearnedhelplessness AT xiaoyanguo neuralplasticityassociatedwithhippocampalpkacrebandnmdasignalingisinvolvedintheantidepressanteffectofrepeatedlowdoseofyuejupillonchronicmousemodeloflearnedhelplessness AT yuxuanzhang neuralplasticityassociatedwithhippocampalpkacrebandnmdasignalingisinvolvedintheantidepressanteffectofrepeatedlowdoseofyuejupillonchronicmousemodeloflearnedhelplessness AT gangchen neuralplasticityassociatedwithhippocampalpkacrebandnmdasignalingisinvolvedintheantidepressanteffectofrepeatedlowdoseofyuejupillonchronicmousemodeloflearnedhelplessness |