Activation of ERK/CREB/BDNF pathway involved in abnormal behavior of neonatally Borna virus-infected rats

Li, Chenmeng; Xu, Xiaoyan; Zhang, Xiong; Cheng, Ke; Guo, Yujie; Jie, Jie; Guo, Hua; He, Yong; Zhou, Chanjuan; Gui, Siwen; Zhong, Xiaogang; Wang, Haiyang

doi:10.2147/ndt.s176399

Cited by 5 publications

(4 citation statements)

References 48 publications

(45 reference statements)

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“…Previous studies demonstrated that the direct phosphorylation of Ser133 in CREB was regulated by multiple upstream pathways and proteins (62,64,65), such as the protein kinase A (PKA) (62,64), ERK1/2 (66,67), phosphoinositide 3-kinase/ protein kinase B (PI3K/AKT) (68), and CaMKII (69,70) signalling pathways. In addition, evidence has accumulated for the involvement of calcium/calmodulin and intracellular Ca 2+ in the pathophysiology of mood disorders (45,47,48), indicating that a supraspinal increase in intracellular calcium contents was involved in the modulation of mood leading to a depressant-like effect in laboratory animals (45), and blocking Ca 2+ release from intracellular stores provoked a decrease in the immobility time inducing an antidepressantlike effect (45,47,48,71).…”

Section: Effects Of Gxdsf On the Expression Levels Of Camkⅱ And Creb/...mentioning

confidence: 99%

Antidepressant-like effects of the Guanxin Danshen formula via mediation of the CaMK II-CREB-BDNF signalling pathway in chronic unpredictable mild stress-induced depressive rats

Xie¹,

Meng²,

Zhai³

et al. 2019

Ann. Transl. Med.

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Background: Depression is a chronic and recurrent syndrome of mood disorder causing immense social and economic burden; thus, treatment should be improved. Guanxin Danshen formula (GXDSF), a natural botanical drug composition prescription, has significant cardiovascular protective effects and is widely used in the clinical treatment of myocardial ischaemic diseases. However, it is still unclear and seldom studied whether GXDSF has neuroprotective effects against depressive disorders. This study explored whether GXDSF has antidepressant-like effects in rats exposed to chronic unpredictable mild stress (CUMS) and analysed the possible underlying neurotrophic expression and psychotropic mechanisms.Methods: The present study was designed to investigate the antidepressant effects of GXDSF treatment in a CUMS-induced rat model. Based on the clinical doses, the drug-treated group was intragastrically administered GXDSF for 30 days, and rats were simultaneously exposed to CUMS stimulation for 30 days.After induction and drug administration, the depression-like behaviours were determined via the sucrose preference test (SPT), the open field test (OFT), the tail suspension test (TST), and the forced swim test (FST). ELISA kits were used to examine the monoaminergic neurotransmitters, monoamine oxidase (MAO) and Ca 2+ levels in the hippocampus. Moreover, we measured and analysed the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels and the upstream regulation and signal pathways of BDNF and NGF to explore their related mechanisms in this animal model of depression, including calciumcalmodulin dependent protein kinase-II (CaMKII) and cAMP response element-binding (CREB). Results:The results revealed that GXDSF may possess significant antidepressant-like effects via improving body weight, raising the sucrose preference in the SPT, increasing the total distance, the number of upright stands, and the residence time of the central zone in the open field test (OPF) and reducing the immobility time in the TST and FST. In addition, GXDSF significantly upregulated the relative levels of neurotransmitters, including dopamine (DA), norepinephrine (NE), and serotonin (5-HT), in a dose-dependent manner and inhibited MAO activities in the hippocampus. Moreover, GXDSF reversed the decline in intracellular CREB and p-CREB expression induced by CUMS, downregulated the phosphorylation levels of intracellular CaMKII and its two subunits CaMKIIα and CaMKIIβ in the hippocampus, and thus, clearly upregulated the downstream effector protein expression levels of BDNF, Xie et al. Guanxin Danshen formula alleviate depression

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Section: Effects Of Gxdsf On the Expression Levels Of Camkⅱ And Creb/...mentioning

confidence: 99%

Antidepressant-like effects of the Guanxin Danshen formula via mediation of the CaMK II-CREB-BDNF signalling pathway in chronic unpredictable mild stress-induced depressive rats

Xie¹,

Meng²,

Zhai³

et al. 2019

Ann. Transl. Med.

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“…15 However, persistently infected rats will have severe hippocampal damage, and slight learning and behavioral impairments can be observed. [13][14][15][16] Our previous studies have shown that BoDV-1 infection can impair the cognitive function of rats, 17,18 but the relevant mechanisms and pathways are still unclear.…”

Section: Introductionmentioning

confidence: 99%

BoDV‐1 infection induces neuroinflammation by activating the TLR4/MyD88/IRF5 signaling pathway, leading to learning and memory impairment in rats

Tang

Guo

et al. 2021

Journal of Medical Virology

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Borna disease virus (BoDV-1) can infect the hippocampus and limbic lobes of newborn rodents, causing cognitive deficits and abnormal behavior. Studies have found that neuroinflammation caused by viral infection in early life can affect brain development and impair learning and memory function, revealing the important role of neuroinflammation in cognitive impairment caused by viral infection. However, there is no research to explore the pathogenic mechanism of BoDV-1 in cognition from the direction of neuroinflammation. We established a BoDV-1 infection model in rats, and tested the learning and memory impairment by Morris water maze (MWM) experiment. RNAseq was introduced to detect changes in the gene expression profile of BoDV-1 infection, focusing on inflammation factors and related signaling pathways. BoDV-1 infection impairs the learning and memory of Sprague-Dawley rats in the MWM test and increases the expression of inflammatory cytokines in the hippocampus. RNAseq analysis found 986 differentially expressed genes (DEGs), of which 845 genes were upregulated and 141 genes were downregulated, and 28 genes were found to be enriched in the toll-like receptor (TLR) pathway. The expression of TLR4, MyD88, and IRF5 in the hippocampus was significantly changed in the BoDV-1 group. Our results indicate that BoDV-1 infection stimulates TLR4/ MyD88/IRF5 pathway activation, causing the release of downstream inflammatory factors, which leads to neuroinflammation in rats. Neuroinflammation may play a significant role in learning and memory impairment caused by BoDV-1 infection.

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“…Given that pinocembrin modulates the ERK–CREB–BDNF pathway in the amygdala and hippocampus, this action might play a pivotal role in anxiety‐related behavior (Figure 6). 46,72,73 Overall, the present work highlights the lack of the studies related to CAPE as well as pinocembrin on anxiety‐like behavior, despite the suggestive evidence.…”

Section: Neuropharmacological Effectsmentioning

confidence: 62%

Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components

Silveira

Luz

Silva

et al. 2020

Medicinal Research Reviews

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Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well‐explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro‐inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.

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Activation of ERK/CREB/BDNF pathway involved in abnormal behavior of neonatally Borna virus-infected rats

Cited by 5 publications

References 48 publications

Antidepressant-like effects of the Guanxin Danshen formula via mediation of the CaMK II-CREB-BDNF signalling pathway in chronic unpredictable mild stress-induced depressive rats

Antidepressant-like effects of the Guanxin Danshen formula via mediation of the CaMK II-CREB-BDNF signalling pathway in chronic unpredictable mild stress-induced depressive rats

BoDV‐1 infection induces neuroinflammation by activating the TLR4/MyD88/IRF5 signaling pathway, leading to learning and memory impairment in rats

Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components

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