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NMDAR Microglia

Lijuan Lu, Cailong Pan, Lu Chen, Liang Hu, Chaoyu Wang, Yuan Han, Zhixiang Cheng, Yanjing Yang, Wen-Tao Liu
Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ (PKCγ), N-methyl-D-aspartate receptor (NMDAR), and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve...
October 15, 2016: Journal of Molecular Cell Biology
Dragos Inta, Undine E Lang, Stefan Borgwardt, Andreas Meyer-Lindenberg, Peter Gass
The implication of neuroinflammation in schizophrenia, sustained by recent genetic evidence, represents one of the most exciting topics in schizophrenia research. Drugs which inhibit microglia activation, especially the classical tetracycline antibiotic minocycline are currently under investigation as alternative antipsychotics. However, recent studies demonstrated that microglia activation is not only a hallmark of neuroinflammation, but plays important roles during brain development. Inhibition of microglia activation by minocycline was shown to induce extensive neuronal cell death and to impair subventricular zone (SVZ) neurogenesis and synaptic pruning in the early postnatal and adolescent rodent brain, respectively...
June 27, 2016: Schizophrenia Bulletin
Zhi Zhang, Bassam Bassam, Ajit G Thomas, Monica Williams, Jinhuan Liu, Elizabeth Nance, Camilo Rojas, Barbara S Slusher, Sujatha Kannan
Astrocyte dysfunction and excessive activation of glutamatergic systems have been implicated in a number of neurologic disorders, including periventricular leukomalacia (PVL) and cerebral palsy (CP). However, the role of chorioamnionitis on glutamate homeostasis in the fetal and neonatal brains is not clearly understood. We have previously shown that intrauterine endotoxin administration results in intense microglial 'activation' and increased pro-inflammatory cytokines in the periventricular region (PVR) of the neonatal rabbit brain...
October 2016: Neurobiology of Disease
Yong-Ku Kim, Kyoung-Sae Na
Treatment-resistant depression (TRD) causes substantial socioeconomic burden. Although a consensus on the definition of TRD has not yet been reached, it is certain that classic monoaminergic antidepressants are ineffective for TRD. One decade ago, many researchers found ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, to be an alternative to classic monoaminergic antidepressants. The major mechanisms of action of ketamine rapidly induce synaptogenesis in the brain-derived neurotrophic factor (BDNF) pathway...
October 3, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
Geetha Kannan, Joshua A Crawford, ChunXia Yang, Kristin L Gressitt, Chinezimuzo Ihenatu, Irina N Krasnova, Jean Lud Cadet, Robert H Yolken, Emily G Severance, Mikhail V Pletnikov
BACKGROUND: Toxoplasma gondii is a pathogen implicated in psychiatric disorders. As elevated antibodies to T. gondii are also present in non-symptomatic individuals, we hypothesized that the age during first exposure to the pathogen may affect symptom manifestation. We tested this hypothesis by evaluating neurobehavioral abnormalities and the immune response in mice following adolescent or adult T. gondii infection. METHODS: Mice were infected with T. gondii at postnatal day 33 (adolescent/juvenile) or 61 (adult)...
July 2016: Neurobiology of Disease
Daniela Punzo, Francesco Errico, Luigia Cristino, Silvia Sacchi, Simona Keller, Carmela Belardo, Livio Luongo, Tommaso Nuzzo, Roberta Imperatore, Ermanno Florio, Vito De Novellis, Ornella Affinito, Sara Migliarini, Giacomo Maddaloni, Maria Josè Sisalli, Massimo Pasqualetti, Loredano Pollegioni, Sabatino Maione, Lorenzo Chiariotti, Alessandro Usiello
The endogenous NMDA receptor (NMDAR) agonist D-aspartate occurs transiently in the mammalian brain because it is abundant during embryonic and perinatal phases before drastically decreasing during adulthood. It is well established that postnatal reduction of cerebral D-aspartate levels is due to the concomitant onset of D-aspartate oxidase (DDO) activity, a flavoenzyme that selectively degrades bicarboxylic D-amino acids. In the present work, we show that d-aspartate content in the mouse brain drastically decreases after birth, whereas Ddo mRNA levels concomitantly increase...
March 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Zheng-Zhen Chen, Dan-Dan Yang, Zhan Zhao, Hui Yan, Juan Ji, Xiu-Lan Sun
AIMS: Memantine is a low-moderate affinity and uncompetitive N-methyl-d-aspartate receptor (NMDAR) antagonist, which is also a potential neuroprotectant in acute ischemic stroke for its particular action profiles. The present study was to reveal the mechanisms involved in the neuroprotection of memantine. MAIN METHODS: We used a mouse model of permanent focal cerebral ischemia via middle cerebral artery occlusion to verify our hypothesis. 2,3,5-Triphenyltetrazolium chloride staining was used to compare infarct size...
April 1, 2016: Life Sciences
D Bravo, C J Maturana, T Pelissier, A Hernández, L Constandil
Pannexin 1 (Panx1) is a glycoprotein that acts as a membrane channel in a wide variety of tissues in mammals. In the central nervous system (CNS) Panx1 is expressed in neurons, astrocytes and microglia, participating in the pathophysiology of some CNS diseases, such as epilepsy, anoxic depolarization after stroke and neuroinflammation. In these conditions Panx1 acts as an important modulator of the neuroinflammatory response, by secreting ATP, by interacting with the P2X7 receptor (P2X7R), and as an amplifier of NMDA receptor (NMDAR) currents, particularly in conditions of pathological neuronal hyperexcitability...
November 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
J Hong, S Sha, L Zhou, C Wang, J Yin, L Chen
Sigma-1 receptor (σ1R) has been reported to be decreased in nigrostriatal motor system of Parkinson's disease patients. Using heterozygous and homozygous σ1R knockout (σ1R+/- and σ1R-/-) mice, we investigated the influence of σ1R deficiency on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-impaired nigrostriatal motor system. The injection of MPTP for 5 weeks in wild-type mice (MPTP-WT mice), but not in σ1R+/- or σ1R-/- mice (MPTP-σ1R+/- or MPTP-σ1R-/- mice), caused motor deficits and ~40% death of dopaminergic neurons in substantia nigra pars compacta with an elevation of N-methyl-d-aspartate receptor (NMDAr) NR2B phosphorylation...
2015: Cell Death & Disease
Chih-Zen Chang, Shu-Chuan Wu, Aij-Lie Kwan, Chih-Lung Lin
OBJECTIVE: Decreased 3'-5'-cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and increased N-methyl-d-aspartate (NMDA) related apoptosis were observed in traumatic brain injury (TBI). It is of interest to examine the effect of magnesium lithospermate B (MLB) on cAMP/PKA pathway and NMDAR in TBI. METHODS: A rodent weight-drop TBI model was used. Administration of MLB was initiated 1 week before (precondition) and 24 hours later (reversal). Cortical homogenates were harvested to measure cAMP (enzyme-linked immunosorbent assay), soluble guanylyl cyclases, PKA and NMDA receptor-2β (Western blot)...
October 2015: World Neurosurgery
Luigia Cristino, Livio Luongo, Marta Squillace, Giovanna Paolone, Dalila Mango, Sonia Piccinin, Elisa Zianni, Roberta Imperatore, Monica Iannotta, Francesco Longo, Francesco Errico, Angelo Luigi Vescovi, Michele Morari, Sabatino Maione, Fabrizio Gardoni, Robert Nisticò, Alessandro Usiello
We have investigated the relevance of d-aspartate oxidase, the only enzyme known to selectively degrade d-aspartate (d-Asp), in modulating glutamatergic system homeostasis. Interestingly, the lack of the Ddo gene, by raising d-Asp content, induces a substantial increase in extracellular glutamate (Glu) levels in Ddo-mutant brains. Consistent with an exaggerated and persistent N-methyl-d-aspartate receptor (NMDAR) stimulation, we documented in Ddo knockouts severe age-dependent structural and functional alterations mirrored by expression of active caspases 3 and 7 along with appearance of dystrophic microglia and reactive astrocytes...
May 2015: Neurobiology of Aging
Ya-Juan Zhao, Yang Liu, Qiang Li, Yin-Hua Zhao, Jian Wang, Min Zhang, Yong-Jin Chen
It is commonly accepted that psychological stress contributes to the development of temporomandibular joint disorders, in which chronic orofacial pain is the main symptom. However, the central mechanism underlying the development of these disorders has remained unclear. The current study was performed to determine the involvement of the glia in the trigeminal spinal subnucleus caudalis in stress-induced increases in masseter muscle hyperalgesia in rats. After being subjected to chronic restraint stress, the animals showed decreased body weight gain, behavioral changes and marked masseter allodynia...
April 1, 2015: Physiology & Behavior
Frank Leypoldt, Romana Höftberger, Maarten J Titulaer, Thaís Armangue, Nuria Gresa-Arribas, Holger Jahn, Kevin Rostásy, Wolfgang Schlumberger, Thomas Meyer, Klaus-Peter Wandinger, Myrna R Rosenfeld, Francesc Graus, Josep Dalmau
IMPORTANCE: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe but treatable autoimmune encephalitis affecting mainly young adults and children. The lack of suitable biomarkers of disease activity makes treatment decisions and identification of relapses challenging. OBJECTIVE: To determine the levels of the B-cell-attracting C-X-C motif chemokine 13 (CXCL13) in serum samples and cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis and whether they can be used as biomarkers of treatment response and outcome...
February 2015: JAMA Neurology
Lasse Dissing-Olesen, Jeffrey M LeDue, Ravi L Rungta, Jasmin K Hefendehl, Hyun B Choi, Brian A MacVicar
Microglia are morphologically dynamic cells that rapidly extend their processes in response to various stimuli including extracellular ATP. In this study, we tested the hypothesis that stimulation of neuronal NMDARs trigger ATP release leading to communication with microglia. We used acute mouse hippocampal brain slices and two-photon laser scanning microscopy to study microglial dynamics and developed a novel protocol for fixation and immunolabeling of microglia processes. Similar to direct topical ATP application in vivo, short multiple applications of NMDA triggered transient microglia process outgrowth that was reversible and repeatable indicating that this was not due to excitotoxic damage...
August 6, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jingfei Zhang, Aqsa Malik, Hyun B Choi, Rebecca W Y Ko, Lasse Dissing-Olesen, Brian A MacVicar
Complement receptor 3 (CR3) activation in microglia is involved in neuroinflammation-related brain disorders and pruning of neuronal synapses. Hypoxia, often observed together with neuroinflammation in brain trauma, stroke, and neurodegenerative diseases, is thought to exacerbate inflammatory responses and synergistically enhance brain damage. Here we show that when hypoxia and an inflammatory stimulus (lipopolysaccharide [LPS]) are combined, they act synergistically to trigger long-term synaptic depression (LTD) that requires microglial CR3, activation of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and GluA2-mediated A-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) internalization...
April 2, 2014: Neuron
Hui-Bin Chen, Fei Li, Shuai Wu, Shu-Cheng An
The present study was to investigate the role of the quinolinic acid (QUIN) and its relationship with N-methyl-D-aspartic acid (NMDA) receptor and metabotropic glutamate receptor 1 (mGluR1) in depression induced by chronic unpredictable mild stress (CUMS) in hippocampus. CUMS-induced depression model was established in Sprague-Dawley rats. Intrahippocampal injections of QUIN, QUIN antagonist Ro61-8048, non-competitive NMDA receptor antagonist MK-801 and mGluR1 antagonist AIDA were respectively adopted by rat brain stereotaxic coordinates...
December 25, 2013: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Maarten Swartjes, Marieke Niesters, Lara Heij, Ann Dunne, Leon Aarts, Carla Cerami Hand, Hyung-Suk Kim, Michael Brines, Anthony Cerami, Albert Dahan
Neuropathic pain (NP) is a debilitating condition associated with traumatic, metabolic, autoimmune and neurological etiologies. Although the triggers for NP are diverse, there are common underlying pathways, including activation of immune cells in the spinal cord and up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Ketamine, a well-known NDMAR antagonist, reduces neuropathic pain in a sustained manner. Recent study has shown that the novel 11-amino acid peptide erythropoietin derivative ARA290 produces a similar, long-lasting relief of NP...
2013: PloS One
Jianming Yang, Dehui Hu, Jianxun Xia, Jianuo Liu, Gang Zhang, Howard E Gendelman, Nawal M Boukli, Huangui Xiong
A plethora of prior studies has linked HIV-1-infected and immune activated brain mononuclear phagocytes (MP; blood borne macrophages and microglia) to neuronal dysfunction. These are modulated by N-methyl-D-aspartate receptor (NMDAR) antagonists and supporting their relevance for HIV-1-associated nervous system disease. The role of NMDAR subsets in HIV-1-induced neuronal injury, nonetheless, is poorly understood. To this end, we investigated conditioned media from HIV-1gp120-treated human monocyte-derived-macrophages (MDM) for its abilities to affect NMDAR-mediated excitatory postsynaptic currents (EPSC(NMDAR)) in rat hippocampal slices...
September 2013: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Xi-Tuan Ji, Nian-Song Qian, Tao Zhang, Jin-Mao Li, Xin-Kui Li, Peng Wang, Dong-Sheng Zhao, Gang Huang, Lei Zhang, Zhou Fei, Dong Jia, Le Niu
Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain enigmatic. Accumulating evidence implicates the involvement of spinal glia in some neuropathic pain models. In this study, using a vincristine-evoked CNP rat model with obvious mechanical allodynia, we found that spinal astrocyte rather than microglia was dramatically activated. The mechanical allodynia was dose-dependently attenuated by intrathecal administratration of L-α-aminoadipate (astrocytic specific inhibitor); whereas minocycline (microglial specific inhibitor) had no such effect, indicating that spinal astrocytic activation contributes to allodynia in CNP rat...
2013: PloS One
Marina Mikhaylova, Anna Karpova, Julia Bär, Philipp Bethge, PingAn YuanXiang, Ying Chen, Werner Zuschratter, Thomas Behnisch, Michael R Kreutz
In previous work, we found that the protein messenger Jacob is involved in N-methyl-D-aspartate receptor (NMDAR) signaling to the nucleus and cAMP response element-binding protein (CREB) mediated gene expression in hippocampal primary neurons. Particularly, extrasynaptic NMDAR activation drives Jacob efficiently into the nucleus where it then induces gene expression that promotes neurodegeneration. However, the protein also translocates to the nucleus in CA1 neurons after Schaffer collateral long-term potentiation (LTP) but not long-term depression (LTD), suggesting that Jacob might be involved in hippocampal and LTP-dependent learning and memory processes...
May 2014: Brain Structure & Function
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