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n-methyl-d-aspartate receptor subunit 1 regulates neurogenesis in the hippocampal dentate gyrus of schizophrenia-like mice

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neural Regeneration Research 2019年第12期14卷 2112-2117页

作者： Juan ding Chun Zhang Yi-Wei Zhang Quan-Rui Ma Yin-Ming Liu Tao Sun Juan Liu ningxia Key Laboratory of Cerebrocranial diseases Institute of Basic Medical Sciences School of Basic Medical Sciences Ningxia Medical University

n-methyl-d-aspartate receptor hypofunction is the basis of pathophysiology in schizophrenia. Blocking the n-methyl-d-aspartate receptor impairs learning and memory abilities and induces pathological changes in the brain. Previous studies have paid little attention to the role of the n-methyl-d-aspartate receptor subunit 1 (nR1) in neurogenesis in the hippocampus of schizophrenia. A mouse model of schizophrenia was established by intraperitoneal injection of 0.6 mg/kg MK-801, once a day, for 14 days. In n-methyl-d-aspartate-treated mice, n-methyl-d-aspartate was administered by intracerebroventricular injection in schizophrenia mice on day 15. The number of nR1-, Ki67- or BrdU-immunoreactive cells in the dentate gyrus was measured by immunofluorescence staining. Our data showed the number of nR1-immunoreactive cells increased along with the decreasing numbers of BrdU- and Ki67-immunoreactive cells in the schizophrenia groups compared with the control group. n-methyl-d-aspartate could reverse the above changes. These results indicated that nR1 can regulate neurogenesis in the hippocampal dentate gyrus of schizophrenia mice, supporting nR1 as a promising therapeutic target in the treatment of schizophrenia. This study was approved by the Experimental Animal Ethics Committee of the ningxia Medical University, China (approval no. 2014-014) on March 6, 2014.

关键词： nerve regeneration schizophrenia MK-801 n-methyl-d-aspartate neurogenesis n-methyl-d-aspartate receptor n-methyl-daspartate receptor subunit 1 BrdU Ki67 hippocampal dentate gyrus hippocampal neurogenesis neural regeneration

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n-methyl-d-aspartate glutamate receptors (nMdARs) in stroke pathogenesis and treatments

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Journal of Translational neuroscience 2019年第4期4卷 1-12页

作者： Wenlin Chen Yang Ge Yutian Wang djavad Mowafaghian Centre for Brain Health and department of Medicine University of British ColumbiaVancouverV6T 2B5Canada

n-methyl-d-aspartate glutamate receptors(nMdARs)play crucial roles in the pathogenesis of neuronal injuries following a stroke insult;therefore,a plethora of preclinical studies focus on better understanding functions of nMdARs and their associated signaling *** the past decades,nMdARs have been found to exert dual effects in neuronal deaths signaling and neuronal survival signaling during cerebral ***,many complex intracellular signaling pathways downstream of nMdAR activation have been elucidated,which provide novel targets for developing much-needed neuro-protectants for patients with *** this review,we will discuss the recent progress in understanding the underlying mechanisms of stroke related to nMdAR activation and the potential therapeutic strategies based on these discoveries.

关键词： n-methyl-d-aspartate glutamate receptors(nMdARs) stroke treatments neuronal survival signaling complex(nSC) neuronal death signaling complex(ndC)

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Cysteinyl leukotriene receptor 1 is involved in n-methyl-d-aspartate-mediated neuronal injury in mice

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Acta Pharmacologica Sinica 2006年第12期27卷 1526-1536页

作者： Qian dInG Er-qing WEI~2 Yan-jun ZHAnG Wei-ping ZHAnG Zhong CHEn department of Pharmacology,School of Medicine,Zhejiang University,Hangzhou 310058,China departmentofPharmacology SchoolofMedicineZhejiangUniversityHangzhou310058China

Aim:To determine whether cysteinyl leukotriene receptor 1(CysLT1receptor)isinvolved in n-methyl-d-aspartate(nMdA)-induced excitotoxic injury in the ***:Brain injury was induced by nMdA microinjection(50-150 nmolin 0.5 μL)into the cerebral *** changes in CysLT1receptor expression24 h after nMdA injection and the effects of a CysLT1receptor antagonist,pranlukast(0.01 and 0.1 mg/kg),an nMdA receptor antagonist,ketamine(30mg/kg),and an antioxidant,edaravone(9 mg/kg)were ***:In thenMdA-injured brain,the CysLT1receptor mRnA,and protein expression wereupregulated,and the receptor was mainly localized in the neurons and not in ***,ketamine and edaravone decreased nMdA-induced injury;pranlukast(0.1 mg/kg)and ketamine inhibited the upregulated expression of ***:CysLT1receptor expression in neurons isupregulated after nMdA injection,and nMdA-induced responses are inhibitedby CysLT1receptor antagonists,indicating that the increased CysLT1receptor isinvolved in nMdA excitotoxicity.

关键词： cysteinyl leukotriene receptor excitotoxicity n-methyl-d-aspartate leukotriene receptor antagonist pranlukast nMdA receptor antagonist ketamine

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Anti-n-methyl-d-aspartate receptor encephalitis in China

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neuroimmunology and neuroinflammation 2014年第1期1卷 17-23页

作者： Li Li Cheng-Bin Wang Gang Zhao department of neurology Xijing HospitalFourth Military Medical UniversityXi’an 710032ShaanxiChina department of Clinical Medicine Fourth Military Medical UniversityXi’an 710032ShaanxiChina

n-methyl-d-aspartate receptors(nMdARs)are mainly distributed in the central nervous system,and play important roles in the mechanisms of learning and memory.A newly discovered disease caused by autoantibody to nMdAR has been described,and is called anti-nMdAR *** with this disease often suffer from mental disorders,seizures and other encephalitis-like *** data suggests that the severity of the disease makes early diagnosis very *** detecting the autoantibody to nMdAR is considered to be the gist of *** prognosis is predicted in most patients,when treated *** is preferred in most *** China,this disease has been reported only for a few years,but sporadic case reports are also helpful for profiling.

关键词： Encephalitis n-methyl-d-aspartate therapy

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How could n-methyl-d-aspartate receptor antagonists lead to excitation instead of inhibition?

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Translational neuroscience and Clinics 2018年第2期4卷 73-98页

作者： Tonghui Su Yi Lu Yang Geng Wei Lu Yelin Chen Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of Chinese Academy of Sciences Beijing 100049China national Institute of neurological disorders and Stroke National Institutes of HealthBethesdaMD 20892USA

n-methyl-d-aspartate receptors(nMdARs) are a family of ionotropic glutamate receptors mainly known to mediate excitatory synaptic transmission and plasticity. Interestingly, low-dose nMdAR antagonists lead to increased, instead of decreased, functional connectivity;and they could cause schizophrenia-and/or antidepressant-like behavior in both humans and rodents. In addition, human genetic evidences indicate that nMdAR loss of function mutations underlie certain forms of epilepsy, a disease featured with abnormal brain hyperactivity. Together, they all suggest that under certain conditions,nMdAR activation actually lead to inhibition, but not excitation,of the global neuronal network. Apparently, these phenomena are rather counterintuitive to the receptor's basic role in mediating excitatory synaptic transmission. How could it happen? Recently, this has become a crucial question in order to fully understand the complexity of nMdAR function, particularly in disease. Over the past decades, different theories have been proposed to address this question. These include theories of "nMdARs on inhibitory neurons are more sensitive to antagonism", or "basal nMdAR activity actually inhibits excitatory synapse", etc. Our review summarizes these efforts, and also provides an introduction of nMdARs,inhibitory neurons, and their relationships with the related *** in the development of novel nMdAR pharmacological tools, particularly positive allosteric modulators, are also included to provide insights into potential intervention strategies.

关键词： n-methyl-d-aspartate receptor synaptic transmission inhibition excitation brain disease positive allosteric modulator

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Chinese Tuina remodels the synaptic structure in neuropathic pain rats by downregulating the expression of n-methyl d-aspartate receptor subtype 2B and postsynaptic density protein-95 in the spinal cord dorsal horn

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中医杂志:英文版 2023年第4期43卷 715-724页

作者： HUAnG Hongye WAnG Bingqian CHEn Shuijin FAnG Jiayu WAnG Xiaohua CHEn Lechun JIAnG Yu ZHAnG Huanzhen CHEn Jincheng LIn Zhigang College of Rehabilitation Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122China Fujian University of Traditional Chinese Medicine Subsidiary Rehabilitation Hospital Fuzhou 350003China Fujian Provincial Key Laboratory of Rehabilitation Technology Fuzhou 350003China Peking University International Hospital Beijing 102206China

OBJECTIVE:To investigate whether the Chinese massage system,Tuina,exerts analgesic effects in a rat model of chronic constriction injury(CCI)by remodeling the synaptic structure in the spinal cord dorsal horn(SCdH).METHOdS:Sixty-nine male Sprague–dawley rats were randomly and evenly divided into the normal group,sham group,CCI group,CCI+Tuina group,CCI+MK-801[an n-methyl d-aspartate receptor subtype 2B(nR2B)antagonist]group,and CCI+MK-801+Tuina *** neuropathic pain model was established using CCI with right sciatic nerve *** was administered 4 d after CCI surgery,using pressing manipulation for 10 min,once *** function was observed with the inclined plate test,and pain behaviors were observed by the Von Frey test and acetone spray *** 19 d after surgery,the L3-L5 spinal cord segments were ***,interleukin 1β(IL-1β),and tumor necrosis factor-α(TnF-α)levels were detected by enzyme-linked immunosorbent *** protein expression levels of nR2B and postsynaptic density protein-95(PSd-95)were detected by Western blot,and the synaptic structure was observed by transmission electron microscopy(TEM).RESULTS:CCI reduced motor function and caused mechanical and cold allodynia in rats,increased glutamate concentration and TnF-αand IL-1βlevels,and increased expression of synapse-related proteins nR2B and PSd-95 in the *** revealed that the synaptic structure of SCdH neurons was *** of these disease-induced changes were reversed by Tuina and intrathecal injection of MK-801(Pnts,no significant differences were found between the CCI+MK-801 and CCI+MK-801+Tuina ***:Chinese Tuina can alleviate pain by remodeling the synaptic structure,and nR2B and PSd-95 receptors in the SCdH may be among its targets.

关键词： neuralgia spinal cord dorsal horn receptors n-methyl-d-aspartate disks large homolog 4 protein neuronal plasticity Chinese Tuina

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Quantitative proteomic and phosphoproteomic analyses of the hippocampus reveal the involvement of nMdAR1 signaling in repetitive mild traumatic brain injury

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neural Regeneration Research 2023年第12期18卷 2711-2719页

作者： Zhicheng Tian Zixuan Cao Erwan Yang Juan Li dan Liao Fei Wang Taozhi Wang Zhuoyuan Zhang Haofuzi Zhang Xiaofan Jiang Xin Li Peng Luo department of neurosurgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina The Sixth Regiment School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina department of neurobiology School of Basic MedicineFourth Military Medical UniversityXi’anShaanxi ProvinceChina Medical Experiment Center Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina department of Anesthesiology The Second Hospital of Jilin UniversityJilin UniversityChangchunJilin ProvinceChina School of Life Science Northwest UniversityXi’anShaanxi ProvinceChina department of Anesthesiology Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina

The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive *** cognitive impairment is thought to result specifically from damage to the *** this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze *** staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain *** staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic *** investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain *** differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain *** contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with *** identified n-methyl-d-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while n-methyl-d-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics *** of GRP78608,an n-methyl-d-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive *** conclusion,our findings

关键词： cognitive impairment Grin1 hippocampus learning memory n-methyl-d-aspartate n-methyl-d-aspartate receptor 1 phosphoproteomic proteomic repetitive mild traumatic brain injury(rmTBI) secondary injury

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neonatal ketamine exposure-induced hippocampal neuroapoptosis in the developing brain impairs adult spatial learning ability

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neural Regeneration Research 2020年第5期15卷 880-886页

作者： dan Lyu ning Tang Andrew W. Womack Yong-Jin He Qing Lin department of Pain Management Tianjin First Center HospitalTianjinChina department of Psychology College of ScienceUniversity of Texas at ArlingtonArlingtonTXUSA Reproductive Medicine Center the 960^th Hospital of the PLA Joint Logistics Support ForceJinanShandong ProvinceChina

Ketamine exposure can lead to selective neuroapoptosis in the developing brain.p66ShcA,the cellular adapter protein expressed selectively in immature neurons,is a known pro-apoptotic molecule that triggers neuroapoptosis when ***-dawley rats at postnatal day 7 were subcutaneously injected in the neck with ketamine 20 mg/kg,six times at 2-hour *** 0,1,3,and 6 hours after final injection,western blot assay was used to detect the expression of cleaved caspase-3,p66ShcA,and phosphorylated *** found that the expression of activated p66ShcA and caspase-3 increased after ketamine exposure and peaked at 3 *** same procedure was performed on a different group of *** the age of 4 weeks,spatial learning and memory abilities were tested with the Morris water *** to find the hidden platform for these rats was longer than it was for control rats,although the residence time in the target quadrant was *** findings indicate that ketamine exposure resulted in p66ShcA being activated in the course of an apoptotic cascade during the neonatal *** may have contributed to the deficit in spatial learning and memory that persisted into *** experimental protocol was approved by the Institutional Animal Care and Use Committee at the University of Texas at Arlington,USA (approval no.A13.008) on January 22,2013.

关键词： caspase-3 developmental neuroapoptosis hippocampus ketamine Morris water maze n-methyl-d-aspartate acid receptors p66ShcA spatial learning

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Magnesium acetyltaurate prevents retinal damage and visual impairment in rats through suppression of nMdA-induced upregulation of nF-κB,p53 and AP-1(c-Jun/c-Fos)

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neural Regeneration Research 2021年第11期16卷 2330-2344页

作者： Lidawani Lambuk Igor Iezhitsa Renu Agarwal Puneet Agarwal Anna Peresypkina Anna Pobeda nafeeza Mohd Ismail Center for neuroscience Research(neuRon) Faculty of MedicineUniversiti Teknologi MARASungai Buloh CampusSelangorMalaysia School of Medicine International Medical UniversityKuala LumpurMalaysia department of Pharmacology and Clinical Pharmacology Institute of MedicineBelgorod State National Research UniversityBelgorodRussia

Magnesium acetyltaurate(MgAT)has been shown to have a protective effect against n-methyl-d-aspartate(nMdA)-induced retinal cell *** current study investigated the involvement of nuclear factor kappa-B(nF-κB),p53 and AP-1 family members(c-Jun/c-Fos)in neuroprotection by MgAT against nMdA-induced retinal *** this study,Sprague-dawley rats were randomized to undergo intravitreal injection of vehicle,nMdA or MgAT as pre-treatment to *** days after injections,retinal ganglion cells survival was detected using retrograde labelling with fluorogold and BRn3A *** outcome of retinal damage was assessed using electroretinography,and the mechanisms underlying antiapoptotic effect of MgAT were investigated through assessment of retinal gene expression of nF-κB,p53 and AP-1 family members(c-Jun/c-Fos)using reverse transcription-polymerase chain *** phospho-nF-κB,phospho-p53 and AP-1 levels were evaluated using western blot *** visual functions were evaluated using visual object recognition *** retrograde labelling and BRn3A immunostaining revealed a significant increase in the number of retinal ganglion cells in rats receiving intravitreal injection of MgAT compared with the rats receiving intravitreal injection of *** indicated that pre-treatment with MgAT partially preserved the functional activity of nMdA-exposed *** abolished nMdA-induced increase of retinal phospho-nF-κB,phospho-p53 and AP-1 expression and suppressed nMdA-induced transcriptional activity of nF-κB,p53 and AP-1 family members(c-Jun/c-Fos).Visual object recognition tests showed that MgAT reduced difficulties in recognizing the visual cues(*** with different shapes)after nMdA exposure,suggesting that visual functions of rats were relatively preserved by pre-treatment with *** conclusion,pre-treatment with MgAT prevents nMdA induced retinal injury by inhibiting nMdA-induced neuronal apoptosis via downr

关键词： AP-1(c-Jun/c-Fos) electroretinography magnesium acetyltaurate neuroprotection nF-κB n-methyl-d-aspartate object recognition tasks p53 retinal excitotoxicity retrograde labelling

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d-serine reduces memory impairment and neuronal damage induced by chronic lead exposure

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neural Regeneration Research 2021年第5期16卷 836-841页

作者： Jian-Zhu Bo Ling Xue Shuang Li Jing-Wen Yin Zheng-Yao Li Xi Wang Jun-Feng Wang Yan-Shu Zhang College of Public Health North China University of Science and TechnologyTangshanHebei ProvinceChina Laboratory Animal Center North China University of Science and TechnologyTangshanHebei ProvinceChina

Although exogenous d-serine has been applied as a neural regulatory intervention in many studies,the role played by d-serine in hippocampal injuries caused by lead exposure remains poorly *** models of chronic lead exposure were established through the administration of 0.05%lead acetate for 8 ***,rats were administered 30 or 60 mg/kg d-serine,intraperitoneally,twice a *** results showed that d-serine treatment shortened the escape latency from the Morris water maze,increased the number of times that mice crossed the original platform location,and alleviated the pathological damage experienced by hippocampal neurons in response to lead *** d-serine administration did not increase the expression levels of the n-methyl-d-aspartate receptor subtype 2B(nR2B)in the hippocampi of lead-exposed rats,60 mg/kg d-serine treatment restored the expression levels of nR2A,which are reduced by lead *** findings suggested that d-serine can alleviate learning and memory impairments induced by lead exposure and that the underlying mechanism is associated with the increased expression of nR2A in the *** study was approved by the Animal Ethics Committee of north China University of Science and Technology,China(approval ***2018155)on december 21,2018.

关键词： d-serine hippocampus lead neurological function n-methyl-d-aspartate poisoning protection repair

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