WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling

Guo, Xin; Chen, Zheng‐Hua; Wang, Huiling; Liu, Zhong‐Chun; Wang, Xiaoping; Zhou, Benhong; Yang, Chaowu; Zhang, Xueping; Xiao, Ling; Shu, Chen; Chen, Jianxin; Wang, Gaohua

doi:10.3892/mmr.2014.3086

Cited by 15 publications

(7 citation statements)

References 32 publications

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“…However, to the best of our knowledge, no decoction has been reported to enhance ERK and CREB signaling in cultured primary neurons. Only until recently, a decoction of thirteen herbs to treat memory impairment of schizophrenia patient was shown to activate ERK and CREB in hippocampi of treated animals [70]. Moreover, PSR likely acts on other targets in addition to NMDAR and ERK/CREB, as all its seven constituent herbs except C. obtusifolia have been implicated to have both anti-oxidative and anti-inflammatory effects, while C. obtusifolia has been implicated to have only anti-inflammatory effect [71–77].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of a novel Chinese herbal decoction on cultured neurons and cerebral ischemic rats

Zhao

Chan

et al. 2016

BMC Complement Altern Med

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BackgroundHistorically, traditional Chinese medicine has been widely used to treat stroke. Based on the theory of Chinese medicine and the modern pharmacological knowledge of herbal medicines, we have designed a neuroprotective formula called Post-Stroke Rehabilitation (PSR), comprising seven herbs – Astragalus membranaceus (Fisch.) Bunge, Salvia miltiorrhiza Bunge, Paeonia lactiflora Pall., Cassia obtusifolia L., Ligusticum chuanxiong Hort., Angelica sinensis (Oliv.) Diels, and Glycyrrhiza uralensis Fisch. We aim to examine the neuroprotective activity of PSR in vitro and in vivo, and to explore the underlying molecular mechanisms, to better understand its therapeutic effect and to further optimize its efficacy.MethodsPSR extract or vehicle was applied to primary rat neurons to examine their survival effects against N-methyl-d-aspartate (NMDA)-elicited excitotoxicity. Whole-cell patch-clamp recording was conducted to examine the NMDA-induced current in the presence of PSR. ERK- and CREB-activation were revealed by western blot analysis. Furthermore, PSR was tested for CRE promoter activation in neurons transfected with a luciferase reporter. The protective effect of PSR was then studied in the rat middle cerebral artery occlusion (MCAO) model. MCAO rats were either treated with PSR extract or vehicle, and their neurobehavioral deficit and cerebral infarct were evaluated. Statistical differences were analyzed by ANOVA or t-test.ResultsPSR prominently reduced the death of cultured neurons caused by NMDA excitotoxicity in a dose-dependent manner, indicating its neuroprotective property. Furthermore, PSR significantly reduced NMDA-evoked current reversibly and activated phosphorylation of ERK and CREB with distinct time courses, with the latter’s kinetics slower. PSR also triggered CRE-promoter activity as revealed by the increased expression of luciferase reporter in transfected neurons. PSR effectively reduced cerebral infarct and deficit in neurological behavior in MCAO rats when PSR decoction was administered starting either 6 days before or 6 h after onset of ischemia.ConclusionsPSR is neuroprotective both in vitro and in vivo – it protects cultured neurons against NMDA excitotoxicity, and effectively reduces ischemic injury and neurobehavioral deficit in MCAO rats in both the pre- and post-treatment regimens. The underlying neuroprotective mechanisms may involve inhibition of NMDA receptor current and activation of ERK and CREB. This study provides important preclinical data necessary for the further development of PSR for stroke treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1417-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Neuroprotective effect of a novel Chinese herbal decoction on cultured neurons and cerebral ischemic rats

Zhao

Chan

et al. 2016

BMC Complement Altern Med

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“…27,34 Decreased phosphorylation of ERK1/2 has been observed in hippocampi exposed to ketamine and chronic multiple stress with impaired learning and memory, 35,36 while upregulation of the MAPK-ERK signaling pathway via drugs can enhance the cognitive performance of mice. 37 Therefore, the decreased level of p-ERK1/2 and increased expression of DUSP2 and PTPN7 (encoding MKP and PTP, activity of which inhibits ERK activity) 38,39 observed in 3.5 nm MPA-modified CdTe QD treatment suggested the inhibition of ERK pathway might be another of the mechanisms of CdTe QD causing impairment in spatial learning and memory in rats.…”

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confidence: 99%

Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms

Wu¹,

He²,

Ang³

et al. 2016

IJN

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With the rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in neuroscience, including basic neurological studies and diagnosis or therapy for neurological disorders, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs, with a growing number of studies. However, knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, even if several studies have attempted to evaluate the toxicity of QDs on neural cells. The aim of this study was to evaluate the adverse effects of intrahippocampal injection in rats of 3-mercaptopropionic acid (MPA)-modified CdTe QDs and underlying mechanisms. First of all, we observed impairments in learning efficiency and spatial memory in the MPA-modified CdTe QD-treated rats by using open-field and Y-maze tests, which could be attributed to pathological changes and disruption of ultrastructure of neurons and synapses in the hippocampus. In order to find the mechanisms causing these effects, transcriptome sequencing (RNA-seq), an advanced technology, was used to gain the potentially molecular targets of MPA-modified CdTe QDs. According to ample data from RNA-seq, we chose the signaling pathways of PI3K–Akt and MPAK–ERK to do a thorough investigation, because they play important roles in synaptic plasticity, long-term potentiation, and spatial memory. The data demonstrated that phosphorylated Akt (p-Akt), p-ERK1/2, and c-FOS signal transductions in the hippocampus of rats were involved in the mechanism underlying spatial learning and memory impairments caused by 3.5 nm MPA-modified CdTe QDs.

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“…Brain derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synapse regulation, learning, and memory through the activation of NMDAR in hippocampus ( Guo et al, 2015 ). The cAMP response element binding protein (CREB) signal pathway is well known to play a critical role in memory formation and participate in the BDNF pathway which elucidates cognitive function regulations in the hippocampus ( Platenik et al, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus

Zhang

Xiao

et al. 2018

Front. Neurosci.

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Background: Pyrethroids have been widely used in residential and agricultural areas. However, little is known about the effects of prenatal exposure to deltamethrin on cognition in early development of offspring. In this study, the effects of prenatal exposure to deltamethrin on learning and memory abilities, N-methyl-D-aspartate receptor (NMDAR) subunits, brain derived neurotrophic factor (BDNF), Tyrosine kinase B (TrkB) receptor, and phosphorylated cAMP response element binding protein (pCREB) in the hippocampus of offspring rats were investigated.Experimental Approaches: Groups each of six female SD rats, as F0-generation, were administered with deltamethrin (0, 0.54, 1.35, and 2.7, 9 mg/kg), or memantine (10 mg/kg), or co-administered with deltamethrin (9 mg/kg) and memantine (10 mg/kg) daily by gavage during pregnancy. The learning and memory ability was evaluated using Morris water maze (MWM) task on postnatal day 21. The expression of NMDAR (GluN1, GluN2A, and GluN2B), BDNF, pTrkB/TrkB, and pCREB/CREB in hippocampus were assessed with western blotting.Results: Prenatal exposure to a relatively low dose of deltamethrin (2.7, 1.35, and 0.54 mg/kg) had no impact on learning and memory abilities or the expression of NMDAR, BDNF, pTrkB, and pCREB in the hippocampus of the exposed offspring. The group treated with 9 mg/kg deltamethrin showed impaired cognitive abilities and decreased expression levels of GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB in the hippocampus. However, the declined cognitive ability were ameliorated by memantine treatment with increased GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB expression in the hippocampus.Conclusion and Implications: Prenatal exposure to a relatively high does of deltamethrin (9 mg/kg) alters cognition in offsprings and that this cognitive dysfunction can be ameliorated by memantine treatment. Moreover, NMDAR/BDNF signaling may be associated with the effects of prenatal exposure to deltamethrin on cognitive ability in offspring.

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WSKY, a traditional Chinese decoction, rescues cognitive impairment associated with NMDA receptor antagonism by enhancing BDNF/ERK/CREB signaling

Cited by 15 publications

References 32 publications

Neuroprotective effect of a novel Chinese herbal decoction on cultured neurons and cerebral ischemic rats

Neuroprotective effect of a novel Chinese herbal decoction on cultured neurons and cerebral ischemic rats

Impairments of spatial learning and memory following intrahippocampal injection in rats of 3-mercaptopropionic acid-modified CdTe quantum dots and molecular mechanisms

Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus

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