Sub-Acute Treatment of Curcumin Derivative J147 Ameliorates Depression-Like Behavior Through 5-HT1A-Mediated cAMP Signaling

作者：Jianxin Li, Ling Chen, Gaowen Li, Xiaojuan Chen, Sisi Hu, Liang Zheng, Victor Luria, Jinpeng Lv, Yindi Sun, Ying Xu, Yingcong Yu · 发表于：Frontiers in Neuroscience · 年份：2020 · DOI：10.3389/fnins.2020.00701 · 被引用次数：27 · 研究领域：Nerve injury and regeneration、Neuroscience and Neuropharmacology Research、Neuropeptides and Animal Physiology

Background: Major 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. Methods: J147 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. Results: The 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...