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https://www.readbyqxmd.com/read/29319606/disruption-of-nnos-nos1ap-protein-protein-interactions-suppresses-neuropathic-pain-in-mice
#1
Wan-Hung Lee, Li-Li Li, Aarti Chawla, Andy Hudmon, Yvonne Y Lai, Michael J Courtney, Andrea G Hohmann
Elevated N-methyl-D-aspartate receptor (NMDAR) activity is linked to central sensitization and chronic pain. However, NMDAR antagonists display limited therapeutic potential due to their adverse side effects. Novel approaches targeting the NR2B-PSD95-nNOS complex to disrupt signaling pathways downstream of NMDARs show efficacy in preclinical pain models. Here, we evaluated the involvement of interactions between neuronal nitric oxide synthase (nNOS) and the nitric oxide synthase 1 adaptor protein (NOS1AP) in pronociceptive signaling and neuropathic pain...
January 9, 2018: Pain
https://www.readbyqxmd.com/read/29305627/antagonism-at-the-nr2b-subunit-of-nmda-receptors-induces-increased-connectivity-of-the-prefrontal-and-subcortical-regions-regulating-reward-behavior
#2
Natalia Gass, Robert Becker, Markus Sack, Adam J Schwarz, Jonathan Reinwald, Alejandro Cosa-Linan, Lei Zheng, Christian Clemm von Hohenberg, Dragos Inta, Andreas Meyer-Lindenberg, Wolfgang Weber-Fahr, Peter Gass, Alexander Sartorius
RATIONALE: Evidence indicates that ketamine's rapid antidepressant efficacy likely results from its antagonism of NR2B-subunit-containing NMDA receptors (NMDAR). Since ketamine equally blocks NR2A- and NR2B-containing NMDAR, and has affinity to other receptors, NR2B-selective drugs might have improved therapeutic efficiency and side effect profile. OBJECTIVES: We aimed to compare the effects of (S)-ketamine and two different types of NR2B-selective antagonists on functional brain networks in rats, in order to find common circuits, where their effects intersect, and that might explain their antidepressant action...
January 5, 2018: Psychopharmacology
https://www.readbyqxmd.com/read/29288339/cdk5-contributes-to-huntington-s-disease-learning-and-memory-deficits-via-modulation-of-brain-region-specific-substrates
#3
Elena Alvarez-Periel, Mar Puigdellívol, Verónica Brito, Florian Plattner, James A Bibb, Jordi Alberch, Silvia Ginés
Cognitive deficits are a major hallmark of Huntington's disease (HD) with a great impact on the quality of patient's life. Gaining a better understanding of the molecular mechanisms underlying learning and memory impairments in HD is, therefore, of critical importance. Cdk5 is a proline-directed Ser/Thr kinase involved in the regulation of synaptic plasticity and memory processes that has been associated with several neurodegenerative disorders. In this study, we aim to investigate the role of Cdk5 in learning and memory impairments in HD using a novel animal model that expresses mutant huntingtin (mHtt) and has genetically reduced Cdk5 levels...
December 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29261550/misaligned-feeding-may-aggravate-pain-by-disruption-of-sleep-awake-rhythm
#4
Fangxia Xu, Xin Zhao, Huan Liu, Xueming Shao, Shuaishuai Chu, Xiangdan Gong, Zhengliang Ma, Xiaoping Gu
BACKGROUND: Increasing evidence suggests that patients with eating disorders are more likely to develop chronic pain. A misaligned diet has been reported to disrupt the sleep-awake rhythms. Combined with our previous investigation on circadian pain, we aimed to investigate the role of misaligned diet in the pain sensitivity and the underlying mechanisms. METHODS: Two-month-old C57BL/6J male mice were administered chronic constriction injury (CCI) surgery to establish neuropathic pain models...
December 19, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29241709/regulation-of-pleiotrophin-and-fyn-in-the-striatum-of-rats-undergoing-l-dopa-induced-dyskinesia
#5
Gimena Gomez, Mariano D Saborido, María A Bernardi, Oscar S Gershanik, Irene R Taravini, Juan E Ferrario
L-DOPA is the gold standard pharmacological therapy for symptomatic treatment of Parkinson's disease (PD), however, its long-term use is associated with the emergence of L-DOPA-induced dyskinesia (LID). Understanding the underlying molecular mechanisms of LID is crucial for the development of newer and more effective therapeutic approaches. In previous publications, we have shown that Pleiotrophin (PTN), a developmentally regulated trophic factor, is up-regulated by L-DOPA in the striatum of dopamine denervated rats...
December 11, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29241651/distinct-roles-of-prelimbic-and-infralimbic-probdnf-in-extinction-of-conditioned-fear
#6
Wei Sun, Xiaoliang Li, Lei An
Brain-derived neurotrophic factor (BDNF) has been investigated for its positive role in regulation of fear acquisition and memory. The precursor of BDNF, proBDNF, has been identified as different protein from its mature form. The prelimbic (PL) and infralimbic (IL) sub-regions of the medial prefrontal cortex (mPFC) are functionally distinct in fear behavior. However, the role of PL and IL proBDNF in fear memory is unclear. Here, through the infusion of cleavage-resistant proBDNF and its antibody, we identified the dissociable roles of PL and IL proBDNF in fear expression and extinction memory as well as explored proBDNF's potential mechanism of action...
December 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29205667/the-effect-of-postnatal-manganese-exposure-on-the-nmda-receptor-signaling-pathway-in-rat-hippocampus
#7
Lei Wang, HuanHuan Fu, Bin Liu, XiaoYan Liu, WeiWei Chen, XiaoDan Yu
Overexposure to manganese (Mn) is associated with neurological disorders in children. Evidence indicated that N-methyl-d-aspartate (NMDA) receptor signaling pathway was critical for neurobehavioral function. However, whether NMDA receptor signaling pathway contributes to Mn-induced neurotoxicity remains unknown. In this study, newborn Sprague-Dawley rats were randomly assigned to four groups exposed to 0, 10, 20, and 30 mg/kg of Mn2+ by intraperitoneal injection (n = 10/group: five males and five females)...
December 4, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29205377/adenosine-a2a-receptors-are-required-for-glutamate-mglur5-and-dopamine-d1-receptor-evoked-erk1-2-phosphorylation-in-rat-hippocampus-involvement-of-nmda-receptor
#8
Paraskevi Krania, Eleni Dimou, Maria Bantouna, Stylianos Kouvaros, Eirini Tsiamaki, Costas Papatheodoropoulos, Konstantinos Sarantis, Fevronia Angelatou
Interaction between mGluR5 and NMDA receptors (NMDAR) is vital for synaptic plasticity and cognition. We recently demonstrated that stimulation of mGluR5 enhances NMDAR-responses in hippocampus by phosphorylating NR2B(Tyr1472) subunit, and this reaction was enabled by adenosine A2A receptors(A2A R) (Sarantis et al.2015). In this study, by using in vitro phosphorylation and western blot analysis in hippocampal slices of male Wistar rats, we show, that mGluR5 stimulation or mGluR5/NMDARs co-stimulation, synergistically activate ERK1/2 signaling leading to c-Fos expression...
December 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29187078/maternal-fluoride-exposure-during-gestation-and-lactation-decreased-learning-and-memory-ability-and-glutamate-receptor-mrna-expressions-of-mouse-pups
#9
Z Sun, Y Zhang, X Xue, R Niu, J Wang
Previous investigations demonstrated that high fluoride (F) exposure may adversely affect the neurodevelopment and learning and memory ability. However, whether maternal F exposure during gestation and lactation can influence the learning, memory ability, and glutamate receptor expressions of offspring has not yet been elucidated. Hence, in the present study, maternal mice were exposed to F (25, 50, or 100 mg/L sodium fluoride (NaF) in drinking water) during gestation and lactation. Results showed that exposure to 100 mg/L NaF significantly enhanced the number of total arm entries and working memory errors of offspring in the radial arm maze test compared to the control group...
January 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29185359/gualou-guizhi-decoction-reverses-brain-damage-with-cerebral-ischemic-stroke-multi-component-directed-multi-target-to-screen-calcium-overload-inhibitors-using-combination-of-molecular-docking-and-protein-protein-docking
#10
Juan Hu, Wen-Sheng Pang, Jing Han, Kuan Zhang, Ji-Zhou Zhang, Li-Dian Chen
Stroke is a disease of the leading causes of mortality and disability across the world, but the benefits of drugs curative effects look less compelling, intracellular calcium overload is considered to be a key pathologic factor for ischemic stroke. Gualou Guizhi decoction (GLGZD), a classical Chinese medicine compound prescription, it has been used to human clinical therapy of sequela of cerebral ischemia stroke for 10 years. This work investigated the GLGZD improved prescription against intracellular calcium overload could decreased the concentration of [Ca2+]i in cortex and striatum neurone of MCAO rats...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29175628/neuronal-death-apoptosis-induced-by-intracellular-zinc-deficiency-associated-with-changes-in-amino-acid-neurotransmitters-and-glutamate-receptor-subtypes
#11
Kun Tian, Yu-Xiang Wang, Li-Xia Li, Yan-Qiang Liu
In the present study, a model of zinc deficiency was developed by exposing primary neurons to an N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN)-containing medium. The cell survival rate, apoptosis rate, intracellular and extracellular concentrations of 4 amino acids, and the expression of 2 glutamate receptor subtypes α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (GluR2)and N-methyl-d-aspartate receptor subtype 2B (NR2B) were evaluated in zinc-deficient cells. The results revealed that zinc deficiency led to a decrease in cell viability and an increase in the apoptosis rate...
November 21, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29139560/the-mammalian-circadian-clock-exhibits-chronic-ethanol-tolerance-and-withdrawal-induced-glutamate-hypersensitivity-accompanied-by-changes-in-glutamate-and-trkb-receptor-proteins
#12
Jonathan H Lindsay, Rebecca A Prosser
BACKGROUND: Alcohol tolerance and withdrawal-induced effects are criteria for alcohol use disorders listed by the DSM-V. Although tolerance and withdrawal have been studied over many decades, there is still uncertainty regarding mechanistic distinctions that characterize these different forms of ethanol (EtOH)-induced plasticity. Previously, we demonstrated that the suprachiasmatic nucleus (SCN) circadian clock develops both acute and rapid tolerance to EtOH inhibition of glutamate-induced circadian phase shifts...
November 15, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29138698/soluble-epoxide-hydrolase-inhibitor-and-14-15-epoxyeicosatrienoic-acid-facilitated-long-term-potentiation-through-camp-and-camkii-in-the-hippocampus
#13
Han-Fang Wu, Yi-Ju Chen, Su-Zhen Wu, Chi-Wei Lee, I-Tuan Chen, Yi-Chao Lee, Chi-Chen Huang, Chung-Hsi Hsing, Chih-Wei Tang, Hui-Ching Lin
Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid and metabolized by soluble epoxide hydrolase (sEH). The role of EETs in synaptic function in the central nervous system is still largely unknown. We found that pharmacological inhibition of sEH to stabilize endogenous EETs and exogenous 14,15-EET significantly increased the field excitatory postsynaptic potential (fEPSP) response in the CA1 area of the hippocampus, while additionally enhancing high-frequency stimulation- (HFS-) induced long-term potentiation (LTP) and forskolin- (FSK-) induced LTP...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29124300/xanthoceraside-modulates-nr2b-containing-nmda-receptors-at-synapses-and-rescues-learning-memory-deficits-in-app-ps1-transgenic-mice
#14
Lin Zhu, Lei Yang, Xuemei Zhao, Danyang Liu, Xiaoli Guo, Peng Liu, Tianyan Chi, Xuefei Ji, Libo Zou
RATIONALE: Alzheimer's disease (AD) is characterized by memory loss and synaptic damage. Previous studies suggested that xanthoceraside decreases glutamate-induced PC12 cell death, ameliorates memory deficits, and increases the number of dendritic spines in AD mice. These results indicated that xanthoceraside might have activities that protect synaptic plasticity. Herein, we detected the effect of xanthoceraside on synaptic function. MATERIALS AND METHODS: Three-month-old APP/PS1 transgenic mice were orally treated with xanthoceraside (0...
November 9, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29116553/effect-of-sinomenine-on-the-morphine-dependence-and-related-neural-mechanisms-in-mice
#15
Miao Fang, Junkui Li, Daoqi Zhu, Chaohua Luo, Chan Li, Chen Zhu, Menglin Fan, Ken Kin-Lam Yung, Zhixian Mo
Evidence suggests that the dopamine receptor rate-limiting enzyme, tyrosine hydroxylase (TH), and the glutamate receptor, N-methyl-D-aspartate receptor 2B (NR2B), contribute to morphine dependence. Previous studies show that chronic exposure to morphine changes the expression of opioid receptors. In this study, we focus on the effects of sinomenine on morphine-dependent mice and its related neural mechanisms. Conditioned place preference (CPP) mouse model was established using morphine (9 mg/kg, s.c.), and their expression levels of TH and NR2B were observed by immunohistochemistry...
December 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29107071/role-of-tlr4-in-olfactory-based-spatial-learning-activity-of-neonatal-mice-after-developmental-exposure-to-diesel-exhaust-origin-secondary-organic-aerosol
#16
Nay Chi Nway, Yuji Fujitani, Seishiro Hirano, Ohn Mar, Tin-Tin Win-Shwe
Exposure to ambient air pollutants has been reported to have various adverse health impacts. Ambient particulate matter comprises primary particles released directly via engine exhaust and secondary organic aerosols (SOAs) formed from oxidative reactions of the ultrafine particle fraction of diesel exhaust (DE). Toll-like receptor 4 (TLR4) is well known to initiate the inflammatory cascade in the central nervous system. However, whether and how DE and DE-SOA exposure influences TLR4 signaling in the immature brain remains unclear...
October 26, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29076975/acute-spinal-cord-injury-diminishes-silent-synapses-in-the-rat-hippocampus
#17
Yingli Jing, Fan Bai, Hui Chen, Hao Dong
Spinal cord injury (SCI) can promote profound functional modification in various brain centers. However, the question of whether SCI can affect the generation of silent synapses that regulate neuronal plasticity in the hippocampus remains unclear. In the present studies, we demonstrated that acute SCI diminished silent synapses in hippocampus of lesioned rats. Furthermore, the SCI induced decline in silent synapses appeared to require the activation of NR2B-containing N-methyl-D-aspartate receptors. Our data show that SCI impaired synaptic plasticity in the hippocampus, suggesting that this region may serve as a potential therapeutic target for meliorating impaired brain functions after SCI...
December 6, 2017: Neuroreport
https://www.readbyqxmd.com/read/29075536/neural-plasticity-associated-with-hippocampal-pka-creb-and-nmda-signaling-is-involved-in-the-antidepressant-effect-of-repeated-low-dose-of-yueju-pill-on-chronic-mouse-model-of-learned-helplessness
#18
Zhilu Zou, Yin Chen, Qinqin Shen, Xiaoyan Guo, Yuxuan Zhang, Gang Chen
Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/29074416/clonidine-preconditioning-improved-cerebral-ischemia-induced-learning-and-memory-deficits-in-rats-via-erk1-2-creb-nf-%C3%AE%C2%BAb-nr2b-pathway
#19
Yanli Li, Min Yu, Bo Zhao, Yan Wang, Yunhong Zha, Zicheng Li, Lingling Yu, Lingling Yan, Zhangao Chen, Wenjuan Zhang, Xiaoli Zeng, Zhi He
Clonidine, a classical α-2 adrenergic agonists, has been shown to antagonize brain damage caused by hypoxia, cerebral ischemia and excitotoxicity and reduce cerebral infarction volume in recent studies. We herein investigate the regulatory effect and possible underlying mechanism of clonidine on learning and memory in rats with cerebral ischemia. The cerebral ischemia rat model was established by right middle cerebral artery occlusion for 2h and reperfusion for 28 days. Drugs were administrated to the rats for consecutive 7 days intraperitoneally and once again on the day of surgery...
October 23, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29059133/a-phase-ib-randomized-controlled-study-to-evaluate-the-effectiveness-of-a-single-dose-of-the-nr2b-selective-n-methyl-d-aspartate-antagonist-mk-0657-on-levodopa-induced-dyskinesias-and-motor-symptoms-in-patients-with-parkinson-disease
#20
W Joseph Herring, Christopher Assaid, Kerry Budd, Ryan Vargo, Ralph S Mazenko, Christopher Lines, Aaron Ellenbogen, Leo Verhagen Metman
OBJECTIVES: Blockade of N-methyl-D-aspartate receptors containing the NR2B subunit has been shown to be therapeutic in animal models of Parkinson disease (PD). However, findings with investigational NR2B receptor antagonists in PD patients have been mixed. The objective of this study was to evaluate the effects of the NR2B selective N-methyl-D-aspartate receptor antagonist MK-0657 on levodopa-induced dyskinesias and motor symptoms in PD patients. METHODS: A randomized, double-blind, single-dose, 2-period crossover study was conducted in 22 patients with PD and levodopa-induced peak-dose dyskinesias...
November 2017: Clinical Neuropharmacology
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