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https://www.readbyqxmd.com/read/27900470/influence-of-the-selective-antagonist-of-the-nr2b-subunit-of-the-nmda-receptor-traxoprodil-on-the-antidepressant-like-activity-of-desipramine-paroxetine-milnacipran-and-bupropion-in-mice
#1
Weronika Stasiuk, Aleksandra Szopa, Anna Serefko, Elżbieta Wyska, Katarzyna Świąder, Jarosław Dudka, Piotr Wlaź, Ewa Poleszak
Pre-clinical and clinical studies indicated that a blockade of the NMDA receptor complex creates new opportunities for the treatment of affective disorders, including depression. The aim of the present study was to assess the influence of traxoprodil (10 mg/kg) on the activity of desipramine (10 mg/kg), paroxetine (0.5 mg/kg), milnacipran (1.25 mg/kg), and bupropion (10 mg/kg), each at sub-therapeutic doses. Moreover, brain levels of traxoprodil and tested agents were determined using HPLC. The obtained results were used to ascertain the nature of occurring interaction between traxoprodil and studied antidepressants...
November 29, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27884727/impact-of-17beta-estradiol-and-progesterone-on-inflammatory-and-apoptotic-microrna-expression-after-ischemia-in-a-rat-model
#2
Rebecca Herzog, Adib Zendedel, Leoni Lammerding, Cordian Beyer, Alexander Slowik
17β-estradiol (E2) and progesterone (P) are neuroprotective factors in the brain preventing neuronal death under different injury paradigms. In previous studies, we demonstrated that both steroids dampen neuronal damage, improve local energy metabolism and attenuate pro-inflammatory responses. MicroRNAs (miRNAs) are small regulators of distinct target genes on the RNA level. Their expression patterns are misbalanced in several neurological disorders. To explore the regulatory mechanisms of steroid hormones on selected miRNAs and their validated targets in ischemia, we used the transient middle cerebral artery occlusion (tMCAO) model...
November 22, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27881347/-effect-of-rhynchophylline-on-behaviors-of-methamphetamine-dependent-zebrafish-and-the-mechanism
#3
Yi-Fei Chen, Ju Peng, Miao Fang, Yi Liu, Ling-Hui Nie, Zhi-Xian Mo, Ling-Ling Zhu
OBJECTIVE: To observe the effect of rhynchophylline on methamphetamine-dependent zebrafish and explore the possible mechanism. METHODS: Zebrafish were divided into control group, amphetamine group, low- (50 mg/kg) and high (100 mg/kg)-dose rhynchophylline groups, and ketamine (150 mg/kg) group. Conditioned place preference (CPP) was induced in zebrafish with methamphetamine, and the staying time in the drug box and the tracking map of the zebrafish were observed with Noldus Ethovision XT system...
November 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27878303/neuroprotective-effects-of-vitexin-against-isoflurane-induced-neurotoxicity-by-targeting-the-trpv1-and-nr2b-signaling-pathways
#4
Linlin Chen, Bin Zhang, Shiqiang Shan, Xin Zhao
Vitexin is a bioactive compound extracted from hawthorn leaves, which reduces blood pressure and has anti‑inflammatory and potential anticancer effects. However, the mechanisms underlying the protective effects of vitexin against isoflurane‑induced neurotoxicity remain elusive. Therefore, the aim of the present study was to investigate these mechanisms further. Sprague Dawley rats received 1.4% isoflurane in a 100% oxygen environment for 2 h. Human PC12 pheochromocytoma neurosecretory cells were exposed to 2% isoflurane for 12 h before they were treated with 1, 10 or 100 µM vitexin for a further 24 h...
November 16, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27876882/nr4a1-knockdown-suppresses-seizure-activity-by-regulating-surface-expression-of-nr2b
#5
Yanke Zhang, Guojun Chen, Baobing Gao, Yunlin Li, Shuli Liang, Xiaofei Wang, Xuefeng Wang, Binglin Zhu
Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871669/induction-and-blockade-of-adolescent-cocaine-induced-habits
#6
Lauren M DePoy, Kelsey S Zimmermann, Paul J Marvar, Shannon L Gourley
BACKGROUND: Cocaine use during adolescence increases vulnerability to drug dependence and decreases the likelihood that individuals will seek treatment as adults. Understanding how early-life cocaine exposure influences decision-making processes in adulthood is thus critically important. METHODS: Adolescent or adult mice were exposed to subchronic cocaine, then behavioral sensitivity to changes in the predictive relationship between actions and their consequences was tested...
October 6, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27871230/effect-of-the-ifenprodil-administered-into-rostral-anterior-cingulate-cortex-on-pain-related-aversion-in-rats-with-bone-cancer-pain
#7
Hao Feng, Zhaowei Chen, Gongming Wang, Xin Zhao, Zhonghao Liu
BACKGROUND: To assess the effect of rostral anterior cingulate cortex (rACC) administration with ifenprodil (NR2B receptor blocker) on bone cancer pain (BCP)-related aversion sentiment using the conditioned place avoidance experiments in rats. METHODS: A total of 30 male Wistar rats without place preference were randomly assigned to three groups: control group (Group C, n = 10), BCP group (Group P, n = 10) and ifenprodil group (Group Ifen, n = 10). Three microliter MADB-106 cells were inoculated into right tibia bone marrow cavity in group P and Ifen, while the same dose of normal saline in group C as a control...
November 21, 2016: BMC Anesthesiology
https://www.readbyqxmd.com/read/27866326/the-neuroprotective-peptide-poly-arginine-12-r12-reduces-cell-surface-levels-of-nmda-nr2b-receptor-subunit-in-cortical-neurons-investigation-into-the-involvement-of-endocytic-mechanisms
#8
Gabriella MacDougall, Ryan S Anderton, Adam B Edwards, Neville W Knuckey, Bruno P Meloni
We have previously reported that cationic poly-arginine and arginine-rich cell-penetrating peptides display high-level neuroprotection and reduce calcium influx following in vitro excitotoxicity, as well as reduce brain injury in animal stroke models. Using the neuroprotective peptides poly-arginine R12 (R12) and the NR2B9c peptide fused to the arginine-rich carrier peptide TAT (TAT-NR2B9c; also known as NA-1), we investigated the mechanisms whereby poly-arginine and arginine-rich peptides reduce glutamate-induced excitotoxic calcium influx...
November 20, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27857754/protective-effect-of-tetrahydroxy-stilbene-glucoside-on-learning-and-memory-by-regulating-synaptic-plasticity
#9
Hong-Bo Luo, Yun Li, Zun-Jing Liu, Li Cao, Zhi-Qiang Zhang, Yong Wang, Xiao-Yan Zhang, Zhao Liu, Xiang-Qun Shi
Damage to synaptic plasticity induced by neurotoxicity of amyloid-beta is regarded to be one of the pathological mechanisms of learning and memory disabilities in Alzheimer's disease patients. This study assumed that the damage of amyloid-beta to learning and memory abilities was strongly associated with the changes in the Fyn/N-methyl-D-aspartate receptor 2B (NR2B) expression. An APP695V7171 transgenic mouse model of Alzheimer's disease was used and treatment with tetrahydroxy-stilbene glucoside was administered intragastrically...
September 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27837332/effects-of-n-methyl-d-aspartate-receptor-ligands-on-sensitivity-to-reinforcer-magnitude-and-delayed-reinforcement-in-a-delay-discounting-procedure
#10
Justin R Yates, Benjamin T Gunkel, Katherine K Rogers, Mallory N Hughes, Nicholas A Prior
RATIONALE: The N-methyl-D-aspartate (NMDA) receptor has been recently identified as an important mediator of impulsive choice, as assessed in delay discounting. Although discounting is independently influenced by sensitivity to reinforcer magnitude and delayed reinforcement, few studies have examined how NMDA receptor ligands differentially affect these parameters. OBJECTIVES: The current study examined the effects of various NMDA receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure...
November 11, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27836791/pharmacological-inhibition-of-pten-attenuates-cognitive-deficits-caused-by-neonatal-repeated-exposures-to-isoflurane-via-inhibition-of-nr2b-mediated-tau-phosphorylation-in-rats
#11
Lei Tan, Xin Chen, Wei Wang, Jianfang Zhang, Shiyong Li, Yilin Zhao, Jintao Wang, Ailin Luo
Evidence has shown that children exposed to repeated anesthesia in early childhood display long-term cognitive disabilities. However, the underlying mechanisms remain largely unclear. Our previous study has indicated the involvement of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in isoflurane-induced decrease of self-renewal capacity in hippocampal neural precursor cells. Additionally, it is demonstrated by others that PTEN inhibition could protect against cognitive impairment via reduction of tau phosphorylation in the alzheimer's disease model...
November 8, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27824163/the-role-of-p2x7-receptors-in-a-rodent-pcp-induced-schizophrenia-model
#12
Bence Koványi, Cecilia Csölle, Stefano Calovi, Adrienn Hanuska, Erzsébet Kató, László Köles, Anindya Bhattacharya, József Haller, Beáta Sperlágh
P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7-/-), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807032/nr2a-containing-nmdars-in-the-prefrontal-cortex-are-required-for-working-memory-and-associated-with-age-related-cognitive-decline
#13
Joseph A McQuail, B Sofia Beas, Kyle B Kelly, Kailey L Simpson, Charles J Frazier, Barry Setlow, Jennifer L Bizon
: Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory. However, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27803647/nr2b-expression-in-rat-drg-is-differentially-regulated-following-peripheral-nerve-injuries-that-lead-to-transient-or-sustained-stimuli-evoked-hypersensitivity
#14
Monica Norcini, Alexandra Sideris, Samantha M Adler, Lourdes A M Hernandez, Jin Zhang, Thomas J J Blanck, Esperanza Recio-Pinto
Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/27781556/mood-therapeutics-novel-pharmacological-approaches-for-treating-depression
#15
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...
October 26, 2016: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/27771532/intrastriatal-injection-of-ionomycin-profoundly-changes-motor-response-to-l-dopa-and-its-underlying-molecular-mechanisms
#16
Chao Han, Shuke Nie, Guiqin Chen, Kai Ma, Nian Xiong, Zhentao Zhang, Yan Xu, Tao Wang, Stella M Papa, Xuebing Cao
Long-term l-DOPA treatment of Parkinson's disease is accompanied with fluctuations of motor responses and l-DOPA-induced dyskinesia (LID). Phosphorylation of the dopamine and c-AMP regulated phosphoprotein of 32kDa (DARPP-32) plays a role in the pathogenesis of LID, and thus dephosphorylation of this protein by activated calcineurin may help reduce LID. One important activator of calcineurin is the Ca(2+) ionophore ionomycin. Here, we investigated whether intrastriatal injection of ionomycin to hemiparkinsonian rats produced changes in l-DOPA responses including LID...
October 19, 2016: Neuroscience
https://www.readbyqxmd.com/read/27732941/negative-regulation-of-rest-on-nr2b-in-spinal-cord-contributes-to-the-development-of-bone-cancer-pain-in-mice
#17
Dan Wang, Jianbo Yu
In this study, C3H/HeNCrlVr mice are implanted with sarcoma NCTC 2472 cells into the intramedullary space of the femur to induce ongoing bone cancer-related pain behaviors. During the progress of the bone cancer pain, the down-regulation in spinal REST (Neuron-restrictive silencer factor, NRSF/REST) with concomitant up-regulation in spinal NR2B (2B subunit of N-methyl-D-aspartate receptor, NR2B) protein expression are observed at days 5, 7, 10 and 14 post-inoculation. Immunofluorescence assay shows that almost all of REST and NR2B-positive signals encompass NeuN (neuron-specific nuclear protein, a neuronal marker)-positive signals in spinal cord of sham and tumor-bearing mice...
July 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27731509/microrna-139-5p-negatively-regulates-nr2a-containing-nmda-receptor-in-the-rat-pilocarpine-model-and-patients-with-temporal-lobe-epilepsy
#18
Walid A Alsharafi, Bo Xiao, Jing Li
OBJECTIVES: Regulation of N-methyl-d-aspartate (NMDA) subunits NR2A and NR2B expression during status epilepticus (SE) remains incompletely understood. Here we explored the role of brain-enriched microRNA (miR)-139-5p in this process. METHODS: miRNA microarray was performed to examine changes in miRNA expression in the rat pilocarpine model following NMDA-receptor blockade. The dynamic expression patterns of miR-139-5p, NR2A, and NR2B levels were measured in rats during the three phases of temporal lobe epilepsy (TLE) development using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot...
November 2016: Epilepsia
https://www.readbyqxmd.com/read/27670903/anticonvulsant-effect-of-rhynchophylline-involved-in-the-inhibition-of-persistent-sodium-current-and-nmda-receptor-current-in-the-pilocarpine-rat-model-of-temporal-lobe-epilepsy
#19
Hui Shao, Yang Yang, Ze Mi, Guang-Xi Zhu, Ai-Ping Qi, Wei-Gang Ji, Zhi-Ru Zhu
Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. Using combined methods of behavioral testing, immunofluorescence and electrophysiological recordings, we characterized the anticonvulsant effect of RIN in a pilocarpine-induced status epilepticus (SE) rat model of temporal lobe epilepsy (TLE) and investigated the underlying cellular mechanisms...
September 23, 2016: Neuroscience
https://www.readbyqxmd.com/read/27664962/n-methyl-d-aspartate-receptor-expression-patterns-in-the-human-fetal-cerebral-cortex
#20
Inseyah Bagasrawala, Fani Memi, Nevena V Radonjić, Nada Zecevic
N-methyl d-aspartate receptors (NMDARs), a subtype of glutamate receptor, have important functional roles in cellular activity and neuronal development. They are well-studied in rodent and adult human brains, but limited information is available about their distribution in the human fetal cerebral cortex. Here we show that 3 NMDAR subunits, NR1, NR2A, and NR2B, are expressed in the human cerebral cortex during the second trimester of gestation, a period of intense neurogenesis and synaptogenesis. With increasing fetal age, expression of the NMDAR-encoding genes Grin1 (NR1) and Grin2a (NR2A) increased while Grin2b (NR2B) expression decreased...
September 24, 2016: Cerebral Cortex
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