Curculigoside facilitates fear extinction and prevents depression-like behaviors in a mouse learned helplessness model through increasing hippocampal BDNF

Abstract

Curculigoside (CUR) is the main active component of traditional Chinese medicine Curculigoorchioides Gaertn (Xianmao in Chinese), which exhibits a variety of pharmacological activities. In this study we investigated the effects of CUR on fear extinction and related depression-like behaviors in mice. In fear conditioning task, we found that administration of CUR (1.6, 8, 40 mg•kg −1 •d −1 , ip, for 7 days) did not affect memory consolidation, but CUR at higher doses (8, 40 mg•kg −1 •d −1) significantly facilitated fear extinction, especially on D3 and D4. Moreover, CUR administration significantly ameliorated the fear conditioning-induced depression-like behaviors, likely through promoting fear extinction. We showed that CUR increased the expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of tropomyosin receptor kinase B (TrkB) in the hippocampus, and activated protein kinase B (Akt)mammalian target of the rapamycin (mTOR) signaling pathway. Administration of the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF, 5 mg•kg −1 •d −1 , ip) also facilitated fear extinction, ameliorated depression-like behaviors. We established a mouse learned helplessness (LH) model to evaluate the antidepressant activity of CUR. The spatial memory was assessed in Morris water maze. We showed that LH-induced depression-like behaviors, including prolonged immobility times in forced swim and tail suspension tests as well as spatial memory impairments; LH also downregulated BDNF expression and the Akt-mTOR signaling pathway in the hippocampus. Administration of CUR (1.6, 8, 40 mg•kg −1 •d −1 , ip, for 14 days) or 7,8-DHF (5 mg•kg −1 •d −1 , ip, for 3 days) prevented LH-induced depression-like behaviors and promoted BDNF expression and the Akt-mTOR signaling pathway. In conclusion, CUR can accelerate the fear memory extinction and ameliorate depression-like behaviors in mice via promoting BDNF expression and activating the Akt-mTOR signaling pathway in the hippocampus.

<p>Effects of Co-Administration of Icariin and <em>Panax notoginseng</em> Saponins on Intestinal Microbiota and Hippocampal Protein Expression in a Mouse Model of Alzheimer’s Disease</p>

“…In can be difficult to observe a clear dosedependent effect when evaluating multiple components or active components from herbal medicine. 25 Surprisingly, the selected dose of donepezil did not promote learning and memory as measured with the MWM. This dose of donepezil may not be sufficient for this specific AD model.…”

<p>Effects of Snake-Derived Phospholipase A2 Inhibitors on Acute Pancreatitis: In vitro and in vivo Characterization</p>

“…PAF and TNF-α levels were detected following the instructions of the assay kits as previously described. 15 The absorbance (OD) was measured at 450 nm wavelength.…”

Botanicals as modulators of depression and mechanisms involved

“…could prevent depression-like behaviors through increasing BDNF expression. At present, our lab also found that curculigoside prevented depression-like activities through increasing hippocampal BDNF level [96]. Interestingly, most of botanicals and active components facilitate BDNF expression through promoting cAMP/PKA/CREB signaling way.…”

“…At present, most of the studies reported BDNF/TrkB signaling pathway as the therapeutic target for depression by the botanicals, which points out the importance of this specific signaling pathway in the pathogenesis of depression [118]. BDNF/TrkB is a crucial synaptic regulator, which not only correlates with memory but also with mood disorders [96, 119]. Therefore, this target should be kept to screen antidepressants.…”