Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling
BackgroundMajor depressive disorder (MDD) is a severe mental disorder related to the deficiency of monoamine neurotransmitters, particularly to abnormalities of 5-HT (5-hydroxytryptamine, serotonin) and its receptors. Our previous study suggested that acute treatment with a novel curcumin derivative...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-07-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2020.00701/full |
| _version_ | 1819019850878550016 |
|---|---|
| author | Jianxin Li Ling Chen Gaowen Li Gaowen Li Xiaojuan Chen Sisi Hu Liang Zheng Victor Luria Jinpeng Lv Jinpeng Lv Yindi Sun Ying Xu Yingcong Yu |
| author_facet | Jianxin Li Ling Chen Gaowen Li Gaowen Li Xiaojuan Chen Sisi Hu Liang Zheng Victor Luria Jinpeng Lv Jinpeng Lv Yindi Sun Ying Xu Yingcong Yu |
| author_sort | Jianxin Li |
| collection | DOAJ |
| description | BackgroundMajor depressive disorder (MDD) is a severe mental disorder related to the deficiency of monoamine neurotransmitters, particularly to abnormalities of 5-HT (5-hydroxytryptamine, serotonin) and its receptors. Our previous study suggested that acute treatment with a novel curcumin derivative J147 exhibited antidepressant-like effects by increasing brain derived neurotrophic factor (BDNF) level in the hippocampus of mice. The present study expanded upon our previous findings and investigated the antidepressant-like effects of sub-acute treatment of J147 for 3 days in male ICR mice and its possible relevancy to 5-HT1A and 5-HT1B receptors and downstream cAMP-BDNF signaling.MethodsJ147 at doses of 1, 3, and 9 mg/kg (via gavage) was administered for 3 days, and the anti-immobility time in the forced swimming and tail suspension tests (FST and TST) was recorded. The radioligand binding assay was used to determine the affinity of J147 to 5-HT1A and 5-HT1B receptor. Moreover, 5-HT1A or 5-HT1B agonist or its antagonist was used to determine which 5-HT receptor subtype is involved in the antidepressant-like effects of J147. The downstream signaling molecules such as cAMP, PKA, pCREB, and BDNF were also measured to determine the mechanism of action.ResultsThe results demonstrated that sub-acute treatment of J147 remarkably decreased the immobility time in both the FST and TST in a dose-dependent manner. J147 displayed high affinity in vitro to 5-HT1A receptor prepared from mice cortical tissue and was less potent at 5-HT1B receptor. These effects of J147 were blocked by pretreatment with a 5-HT1A antagonist NAD-299 and enhanced by a 5-HT1A agonist 8-OH-DPAT. However, 5-HT1B receptor antagonist NAS-181 did not appreciably alter the effects of J147 on depression-like behaviors. Moreover, pretreatment with NAD-299 blocked J147-induced increases in cAMP, PKA, pCREB, and BDNF expression in the hippocampus, while 8-OH-DPAT enhanced the effects of J147 on these proteins’ expression.ConclusionThe results suggest that J147 induces rapid antidepressant-like effects during a 3-day treatment period without inducing drug tolerance. These effects might be mediated by 5-HT1A-dependent cAMP/PKA/pCREB/BDNF signaling. |
| first_indexed | 2024-12-21T03:41:52Z |
| format | Article |
| id | doaj.art-6cf70e1db7e0483097bfa4a9b96e29e7 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-21T03:41:52Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-6cf70e1db7e0483097bfa4a9b96e29e72022-12-21T19:17:11ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2020-07-011410.3389/fnins.2020.00701548466Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP SignalingJianxin Li0Ling Chen1Gaowen Li2Gaowen Li3Xiaojuan Chen4Sisi Hu5Liang Zheng6Victor Luria7Jinpeng Lv8Jinpeng Lv9Yindi Sun10Ying Xu11Yingcong Yu12Department of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, ChinaDepartment of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaNingbo College of Health Sciences, Ningbo, ChinaDepartment of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United StatesDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, ChinaDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, ChinaDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, ChinaDepartment of Systems Biology, Harvard Medical School, Boston, MA, United StatesDepartment of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United StatesCollege of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, ChinaDepartment of Traditional Medical Orthopedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an, ChinaDepartment of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United StatesDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People’s Hospital, Wenzhou, ChinaBackgroundMajor depressive disorder (MDD) is a severe mental disorder related to the deficiency of monoamine neurotransmitters, particularly to abnormalities of 5-HT (5-hydroxytryptamine, serotonin) and its receptors. Our previous study suggested that acute treatment with a novel curcumin derivative J147 exhibited antidepressant-like effects by increasing brain derived neurotrophic factor (BDNF) level in the hippocampus of mice. The present study expanded upon our previous findings and investigated the antidepressant-like effects of sub-acute treatment of J147 for 3 days in male ICR mice and its possible relevancy to 5-HT1A and 5-HT1B receptors and downstream cAMP-BDNF signaling.MethodsJ147 at doses of 1, 3, and 9 mg/kg (via gavage) was administered for 3 days, and the anti-immobility time in the forced swimming and tail suspension tests (FST and TST) was recorded. The radioligand binding assay was used to determine the affinity of J147 to 5-HT1A and 5-HT1B receptor. Moreover, 5-HT1A or 5-HT1B agonist or its antagonist was used to determine which 5-HT receptor subtype is involved in the antidepressant-like effects of J147. The downstream signaling molecules such as cAMP, PKA, pCREB, and BDNF were also measured to determine the mechanism of action.ResultsThe results demonstrated that sub-acute treatment of J147 remarkably decreased the immobility time in both the FST and TST in a dose-dependent manner. J147 displayed high affinity in vitro to 5-HT1A receptor prepared from mice cortical tissue and was less potent at 5-HT1B receptor. These effects of J147 were blocked by pretreatment with a 5-HT1A antagonist NAD-299 and enhanced by a 5-HT1A agonist 8-OH-DPAT. However, 5-HT1B receptor antagonist NAS-181 did not appreciably alter the effects of J147 on depression-like behaviors. Moreover, pretreatment with NAD-299 blocked J147-induced increases in cAMP, PKA, pCREB, and BDNF expression in the hippocampus, while 8-OH-DPAT enhanced the effects of J147 on these proteins’ expression.ConclusionThe results suggest that J147 induces rapid antidepressant-like effects during a 3-day treatment period without inducing drug tolerance. These effects might be mediated by 5-HT1A-dependent cAMP/PKA/pCREB/BDNF signaling.https://www.frontiersin.org/article/10.3389/fnins.2020.00701/fullJ147antidepressant-like effects5-HT1A5-HT1BcAMP/PKABDNF |
| spellingShingle | Jianxin Li Ling Chen Gaowen Li Gaowen Li Xiaojuan Chen Sisi Hu Liang Zheng Victor Luria Jinpeng Lv Jinpeng Lv Yindi Sun Ying Xu Yingcong Yu Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling Frontiers in Neuroscience J147 antidepressant-like effects 5-HT1A 5-HT1B cAMP/PKA BDNF |
| title | Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling |
| title_full | Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling |
| title_fullStr | Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling |
| title_full_unstemmed | Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling |
| title_short | Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling |
| title_sort | sub acute treatment of curcumin derivative j147 ameliorates depression like behavior through 5 ht1a mediated camp signaling |
| topic | J147 antidepressant-like effects 5-HT1A 5-HT1B cAMP/PKA BDNF |
| url | https://www.frontiersin.org/article/10.3389/fnins.2020.00701/full |
| work_keys_str_mv | AT jianxinli subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT lingchen subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT gaowenli subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT gaowenli subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT xiaojuanchen subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT sisihu subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT liangzheng subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT victorluria subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT jinpenglv subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT jinpenglv subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT yindisun subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT yingxu subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling AT yingcongyu subacutetreatmentofcurcuminderivativej147amelioratesdepressionlikebehaviorthrough5ht1amediatedcampsignaling |