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https://www.readbyqxmd.com/read/29074619/presynaptic-mglur5-receptor-controls-glutamatergic-input-through-protein-kinase-c-nmda-receptors-in-paclitaxel-induced-neuropathic-pain
#1
Jing-Dun Xie, Shao-Rui Chen, Hui-Lin Pan
Chemotherapeutic drugs such as paclitaxel cause painful peripheral neuropathy in many cancer patients and survivors. Although NMDA receptors (NMDARs) at primary afferent terminals are known to be critically involved in chemotherapy-induced chronic pain, the upstream signaling mechanism that leads to presynaptic NMDAR activation is unclear. Group I metabotropic glutamate receptors (mGluRs) play a role in synaptic plasticity and NMDAR regulation. Here we report that the Group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of monosynaptic EPSCs evoked from the dorsal root...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29071990/-effect-of-electroacupuncture-intervention-on-expression-of-synaptic-plasticity-related-molecules-in-amygdala-in-chronic-pain-negative-affection-rats
#2
Cheng-Lin Duanmu, Xiu-Mei Feng, Ya-Xia Yan, Jun-Ying Wang, Yong-Hui Gao, Li-Na Qiao, Shu-Ping Chen, Jian-Liang Zhang, Jun-Ling Liu
OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of synaptic plasticity-related glutamate N-methyl-D-aspartate (NMDA) receptor subunit NR 1, gamma-aminobutyric acid (GABA) receptor subunits (Aβ 2, B 1), etc. in the amygdala in chronic neuropathic pain negative affection (CNPPNA) rats, so as to reveal its mechanism underlying pain relief. METHODS: Male Wistar rats were randomized into normal control, CNPPNA model, EA, and anesthesia+EA (AEA)groups (n=14 in each group, 8 for quantitative RT-PCR and 6 for immunofluorescence staining)...
February 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29022871/a-postmortem-analysis-of-nmda-ionotropic-and-group-1-metabotropic-glutamate-receptors-in-the-nucleus-accumbens-in-schizophrenia
#3
Jeremy S Lum, Samuel J Millard, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
BACKGROUND: The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort. METHODS: We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms)...
October 6, 2017: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/28487223/obesogenic-diet-intake-during-pregnancy-programs-aberrant-synaptic-plasticity-and-addiction-like-behavior-to-a-palatable-food-in-offspring
#4
Alberto Camacho, Larisa Montalvo-Martinez, Robbi E Cardenas-Perez, Lizeth Fuentes-Mera, Lourdes Garza-Ocañas
Contextual food conditioned behaviors require plasticity of glutamatergic neurotransmission in the reward system, involving changes in the expression of including a-amino-3-hydroxy-5-methylisoxazole 4-propionate receptors (AMPA), N-methyl-d-aspartic acid (NMDA) and metabotropic glutamate 2,3 (mGlur 2,3). However, the role of changes in glutamatergic synaptic markers on energy-dense palatable food preference during development has not been described. Here, we determine the effect of nutritional programing during gestation on fat food choices using a conditioned place preference (CPP) test and an operant training response and its effect on glutamatergic markers in the nucleus accumbens (Nac) shell and prefrontal cortex (PFC)...
May 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28419871/short-term-inhibition-of-gabaergic-ipscs-induced-by-association-of-pre-and-postsynaptic-activation-in-the-neonatal-hippocampus
#5
Megumi Taketo, Hiroko Matsuda
Activity-dependent plasticity including short and long-term depression accompanied by a reduction in transmitter release probability has been demonstrated in both inhibitory and excitatory synapses. In the neonatal hippocampus, repetitive postsynaptic depolarization is followed by presynaptic alterations of the efficacy of GABAAergic transmission. Both facilitation and inhibition have been observed, but the mechanisms underlying this plasticity have not yet been elucidated. In the present experiment, repetitive postsynaptic depolarization by itself did not cause marked alterations of spontaneous inhibitory postsynaptic currents (sIPSCs)...
July 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28322276/identifying-fast-onset-antidepressants-using-rodent-models
#6
REVIEW
M J Ramaker, S C Dulawa
Depression is a leading cause of disability worldwide and a major contributor to the burden of suicide. A major limitation of classical antidepressants is that 2-4 weeks of continuous treatment is required to elicit therapeutic effects, prolonging the period of depression, disability and suicide risk. Therefore, the development of fast-onset antidepressants is crucial. Preclinical identification of fast-onset antidepressants requires animal models that can accurately predict the delay to therapeutic onset. Although several well-validated assay models exist that predict antidepressant potential, few thoroughly tested animal models exist that can detect therapeutic onset...
May 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28188217/hebbian-spike-timing-dependent-plasticity-at-the-cerebellar-input-stage
#7
Martina Sgritta, Francesca Locatelli, Teresa Soda, Francesca Prestori, Egidio Ugo D'Angelo
Spike-timing-dependent plasticity (STDP) is a form of long-term synaptic plasticity exploiting the time relationship between postsynaptic action potentials (APs) and EPSPs. Surprisingly enough, very little was known about STDP in the cerebellum, although it is thought to play a critical role for learning appropriate timing of actions. We speculated that low-frequency oscillations observed in the granular layer may provide a reference for repetitive EPSP/AP phase coupling. Here we show that EPSP-spike pairing at 6 Hz can optimally induce STDP at the mossy fiber-granule cell synapse in rats...
March 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28134447/t-type-calcium-channels-contribute-to-nmda-receptor-independent-synaptic-plasticity-in-hippocampal-regular-spiking-oriens-alveus-interneurons
#8
Elizabeth Nicholson, Dimitri M Kullmann
KEY POINTS: Regular-spiking interneurons in the hippocampal stratum oriens exhibit a form of long-term potentiation of excitatory transmission that is independent of NMDA receptors but requires co-activation of Ca(2+) -permeable AMPA receptors and group I metabotropic glutamate receptors. We show that T-type Ca(2+) channels are present in such interneurons. Blockade of T-type currents prevents the induction of long-term potentiation, and also interferes with long-lasting potentiation induced either by postsynaptic trains of action potentials or by pairing postsynaptic hyperpolarization with activation of group I metabotropic receptors...
June 1, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27940363/evidence-for-presynaptically-silent-synapses-in-the-immature-hippocampus
#9
Jae Young Yoon, Sukwoo Choi
Silent synapses show NMDA receptor (NMDAR)-mediated synaptic responses, but not AMPAR-mediated synaptic responses. A prevailing hypothesis states that silent synapses contain NMDARs, but not AMPARs. However, alternative presynaptic hypotheses, according to which AMPARs are present at silent synapses, have been proposed; silent synapses show slow glutamate release via a fusion pore, and glutamate spillover from the neighboring synaptic terminals. Consistent with these presynaptic hypotheses, the peak glutamate concentrations at silent synapses have been estimated to be ≪170 μM, much lower than those seen at functional synapses...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27781556/mood-therapeutics-novel-pharmacological-approaches-for-treating-depression
#10
REVIEW
Ioline D Henter, Rafael T de Sousa, Philip W Gold, Andre R Brunoni, Carlos A Zarate, Rodrigo Machado-Vieira
Real-world effectiveness trials suggest that antidepressant efficacy is limited in many patients with mood disorders, underscoring the urgent need for novel therapeutics to treat these disorders. Areas covered: Here, we review the clinical evidence supporting the use of novel modulators for the treatment of mood disorders, including specific glutamate modulators such as: 1) high-trapping glutamatergic modulators; 2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists; 3) NMDA receptor glycine-site partial agonists; and 4) metabotropic glutamate receptor (mGluR) modulators...
February 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27659109/impaired-bidirectional-nmda-receptor-dependent-synaptic-plasticity-in-the-dentate-gyrus-of-adult-female-fmr1-heterozygous-knockout-mice
#11
S Y Yau, C A Bostrom, J Chiu, C J Fontaine, S Sawchuk, A Meconi, R C Wortman, E Truesdell, A Truesdell, C Chiu, B N Hryciw, B D Eadie, M Ghilan, B R Christie
Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmr1 gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmr1 gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits...
September 19, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27633915/a-novel-form-of-capsaicin-modified-amygdala-ltd-mediated-by-trpm1
#12
Christine Gebhardt, Oliver von Bohlen Und Halbach, Michael D Hadler, Christian Harteneck, Doris Albrecht
Recently we have shown that capsaicin attenuates the strength of LTP in the lateral amygdala (LA) and demonstrated that this effect is mediated by the transient receptor potential (TRP) channel TRPV1. Here we further show that capsaicin, which is thought to act primarily through TRPV1, modifies long term depression (LTD) in the LA. Yet the application of various TRPV1 antagonists does not reverse this effect and it remains in TRPV1-deficient mice. In addition, voltage gated calcium channels, nitric oxide and CB1 receptors are not involved...
December 2016: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27546508/-glutamate-receptor-mediated-retinal-neuronal-injury-in-experimental-glaucoma
#13
REVIEW
Zhong-Feng Wang, Xiong-Li Yang
Glaucoma, the second leading cause of blindness, is a neurodegenerative disease characterized by optic nerve degeneration related to apoptotic death of retinal ganglion cells (RGCs). In the pathogenesis of RGC death following the onset of glaucoma, functional changes of glutamate receptors are commonly regarded as important risk factors. During the past several years, we have explored the mechanisms underlying RGC apoptosis and retinal Müller cell reactivation (gliosis) in a rat chronic ocular hypertension (COH) model...
August 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/27411166/metabotropic-glutamate-receptor-5-responses-dictate-differentiation-of-neural-progenitors-to-nmda-responsive-cells-in-fragile-x-syndrome
#14
Venkat Swaroop Achuta, Heli Grym, Noora Putkonen, Verna Louhivuori, Virve Kärkkäinen, Jari Koistinaho, Laurent Roybon, Maija L Castrén
Disrupted metabotropic glutamate receptor 5 (mGluR5) signaling is implicated in many neuropsychiatric disorders, including autism spectrum disorder, found in fragile X syndrome (FXS). Here we report that intracellular calcium responses to the group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) are augmented, and calcium-dependent mGluR5-mediated mechanisms alter the differentiation of neural progenitors in neurospheres derived from human induced pluripotent FXS stem cells and the brains of mouse model of FXS...
April 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/27323449/-ischemic-stroke-excitatory-amino-acids-toxicity-and-the-adjustment-of-acupuncture-intervention
#15
REVIEW
Xiao-xiao Li, Sheng-feng Lu, Bing-mei Zhu, Shu-ping Fu
Excitatory amino acids toxicity is an onset causation of cerebral ischemia injury cascade reaction, and eventually leading to brain cell necrosis and apoptosis. Acupuncture is reported to be effective for ischemic stroke in clinical practice and animal experiments, but its mechanism is still under exploring. In this paper the authors introduce the research status of antiexcitatory amino acids toxicity effect of acupuncture in ischemic stroke animals by summarizing its effects on subunits of ionotropic glutamate receptor (NMDA/AMPA) and metabotropic glutamate receptors (mGluRs), and on astrocyte activities...
April 2016: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/27296639/group-i-mglur-induced-ltd-of-nmdar-synaptic-transmission-at-the-schaffer-collateral-but-not-temperoammonic-input-to-ca1
#16
REVIEW
Stephen Fitzjohn, Zafar Bashir, Paul Farrow
NMDA receptors are composed of multiple subunits and are crucial in the induction of synaptic plasticity and learning and memory. In this study, application of the group I mGlu receptor agonist, DHPG, caused LTD of NMDA-EPSCs (DHPG-LTDNMDA) of the Schaffer collateral, but not of NMDA-EPSCs of the temperoammonic pathway onto CA1 neurons of the hippocampus. DHPGLTDNMDA did not alter the sensitivity of NMDA-EPSC to the GluN2B-antagonist, Ro25-6981, indicating that the postsynaptic NMDA receptor subunit composition remained unchanged following DHPG-LTDNMDA...
2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/26997505/therapeutic-modulation-of-glutamate-receptors-in-major-depressive-disorder
#17
REVIEW
Brittany A Jaso, Mark J Niciu, Nicolas D Iadarola, Niall Lally, Erica M Richards, Minkyung Park, Elizabeth D Ballard, Allison C Nugent, Rodrigo Machado-Vieira, Carlos A Zarate
Current pharmacotherapies for major depressive disorder (MDD) have a distinct lag of onset that can prolong distress and impairment for patients, and realworld effectiveness trials further suggest that antidepressant efficacy is limited in many patients. All currently approved antidepressant medications for MDD act primarily through monoaminergic mechanisms, e.g., receptor/reuptake agonists or antagonists with varying affinities for serotonin, norepinephrine, or dopamine. Glutamate is the major excitatory neurotransmitter in the central nervous system, and glutamate and its cognate receptors are implicated in the pathophysiology of MDD, as well as in the development of novel therapeutics for this disorder...
2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/26843652/metabotropic-glutamate-receptors-induce-a-form-of-ltp-controlled-by-translation-and-arc-signaling-in-the-hippocampus
#18
Hui Wang, Alvaro O Ardiles, Sunggu Yang, Trinh Tran, Rafael Posada-Duque, Gonzalo Valdivia, Min Baek, Yang-An Chuang, Adrian G Palacios, Michela Gallagher, Paul Worley, Alfredo Kirkwood
UNLABELLED: Activity-dependent bidirectional modifications of excitatory synaptic strength are essential for learning and storage on new memories. Research on bidirectional synaptic plasticity has largely focused on long-term potentiation (LTP) and long-term depression (LTD) mechanisms that rely on the activation of NMDA receptors. In principle, metabotropic glutamate receptors (mGluRs) are also suitable to convert synaptic activity into intracellular signals for synaptic modification...
February 3, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26836139/slow-synaptic-transmission-mediated-by-trpv1-channels-in-ca3-interneurons-of-the-hippocampus
#19
Noriomi Eguchi, Akitoyo Hishimoto, Ichiro Sora, Masahiro Mori
Metabotropic glutamate receptors (mGluRs) modulate various neuronal functions in the central nervous system. Many studies reported that mGluRs have linkages to neuronal disorders such as schizophrenia and autism related disorders, indicating that mGluRs are involved in critical functions of the neuronal circuits. To study this possibility further, we recorded mGluR-induced synaptic responses in the interneurons of the CA3 stratum radiatum using rat hippocampal organotypic slice cultures. Electrical stimulation in the CA3 pyramidal cell layer evoked a slow inward current in the interneurons at a holding potential of -70mV in the presence of antagonists for AMPA/kainate receptors, NMDA receptors, GABAA receptors and GABAB receptors...
March 11, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/26824031/novel-glutamatergic-treatments-for-severe-mood-disorders
#20
Minkyung Park, Mark J Niciu, Carlos A Zarate
All currently approved antidepressant medications for major depressive disorder (MDD) and bipolar disorder act primarily on the monoaminergic system and have varying affinities for serotonergic, norepinephrine-ergic, and/or dopaminergic receptors. Unfortunately, these drugs are only effective in approximately two-thirds of patients. Glutamate is the major excitatory neurotransmitter in the central nervous system, and the glutamatergic system has been implicated in the pathophysiology of MDD. Here, we review the putative involvement of the glutamate receptor subtypes-N-methyl-D-aspartate (NMDA), α-amino-3-hydroxyl-5-methyl-4-isoxazoleproprionic acid (AMPA), kainate, and the group I, II, and III metabotropic glutamate receptors (mGluRs)-in the development of novel and more effective treatments for MDD as well as preclinical and clinical trials of drugs targeting these receptors...
December 2015: Current Behavioral Neuroscience Reports
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