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https://www.readbyqxmd.com/read/29736744/antidepressant-efficacy-and-tolerability-of-ketamine-and-esketamine-a-critical-review
#1
REVIEW
P Molero, J A Ramos-Quiroga, R Martin-Santos, E Calvo-Sánchez, L Gutiérrez-Rojas, J J Meana
Ketamine and its enantiomer S-ketamine (esketamine) are promising candidates to produce a rapid-onset antidepressant effect in treatment-resistant depression. Ketamine causes continued blockade of the glutamate N-methyl-D-aspartate (NMDA) receptor, though this might not primarily mediate the antidepressant effect. Alternative hypotheses include selectivity for the NMDA receptor subtype containing the NMDA receptor subunit 2B (NR2B), inhibition of the phosphorylation of the eukaryotic elongation factor 2 (eEF2) kinase, increased expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB), and activation of the mammalian target of rapamycin (mTOR) signaling pathway, alongside other independent actions attributed to the ketamine metabolism to R-hydroxynorketamine (R-HNK)...
May 7, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29695955/glyx-13-ameliorates-schizophrenia-like-phenotype-induced-by-mk-801-in-mice-role-of-hippocampal-nr2b-and-disc1
#2
Dongsheng Zhou, Dan Lv, Zhen Wang, Yanhua Zhang, Zhongming Chen, Chuang Wang
Background: Evidence supports that the hypofunction of N -methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N -Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29665767/nano-cuo-impairs-spatial-cognition-associated-with-inhibiting-hippocampal-ltp-via-affecting-glutamatergic-neurotransmission-in-rats
#3
Xiaoliang Li, Wei Sun, Lei An
Manufactured metal nanoparticles and their applications are continuously expanding because of their unique characteristics while their increasing use may predispose to potential health problems. Several studies have reported the adverse effects of copper oxide nanoparticles (nano-CuO) relative to ecotoxicity and cell toxicity, whereas little is known about the neurotoxicity of nano-CuO. The present study aimed to examine its effects on spatial cognition, hippocampal function, and the possible mechanisms. Male Wistar rats were used to establish an animal model, and nano-CuO was administered at a dose of 0...
January 1, 2018: Toxicology and Industrial Health
https://www.readbyqxmd.com/read/29628771/activation-of-spinal-dorsal-horn-p2y-13-receptors-can-promote-the-expression-of-il-1%C3%AE-and-il-6-in-rats-with-diabetic-neuropathic-pain
#4
Rui Zhou, Tao Xu, XiaoHong Liu, YuanShou Chen, DeYing Kong, Hong Tian, Mingxia Yue, Dujuan Huang, Junwei Zeng
Objective: The dorsal horn P2Y13 receptor is involved in the development of pain behavior induced by peripheral nerve injury. It is unclear whether the expression of proinflammatory cytokines interleukin (IL)-1β and IL-6 at the spinal dorsal horn are influenced after the activation of P2Y13 receptor in rats with diabetic neuropathic pain (DNP). Methods: A rat model of type 1 DNP was induced by intraperitoneal injection of streptozotocin (STZ). We examined the expression of P2Y13 receptor, Iba-1, IL-1β, IL-6, JAK2, STAT3, pTyr1336 , and pTyr1472 NR2B in rat spinal dorsal horn...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29623145/water-soluble-polymer-assists-n-methyl-d-aspartic-acid-receptor-2b-sirna-delivery-to-relieve-chronic-inflammatory-pain-in-vitro-and-in-vivo
#5
Jie Peng, Jiahui Ma, Xue Yang, Huan He, Haopeng Wu, Tongtong Ma, Jianhua Lu
We constructed a water-soluble lipopolymer (WSLP) as a nonviral gene carrier to deliver siRNA targeting NR2B. The cytotoxicity and serum stability of WSLP loaded with siRNA were evaluated, and the knockdown efficiency of WSLP/NR2B-siRNA in PC12 cells was examined. The results showed that WSLP could protect the loading siRNAs from enzymatic degradation in serum and exhibit low cytotoxicity to cells. After transfection, WSLP/NR2B-siRNA complexes reduced the NR2B transcriptional level by 50% and protein level by 55% compared to control siRNA...
2018: Pain Research & Management: the Journal of the Canadian Pain Society
https://www.readbyqxmd.com/read/29617377/inositol-1-4-5-trisphosphate-3-kinase-a-overexpressed-in-mouse-forebrain-modulates-synaptic-transmission-and-mglur-ltd-of-ca1-pyramidal-neurons
#6
Byungil Choi, Hyun Woo Lee, Seojung Mo, Jin Yong Kim, Hyun Wook Kim, Im Joo Rhyu, Eunhwa Hong, Yeon Kyung Lee, June-Seek Choi, Chong-Hyun Kim, Hyun Kim
Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) regulates the level of the inositol polyphosphates, inositol trisphosphate (IP3) and inositol tetrakisphosphate to modulate cellular signaling and intracellular calcium homeostasis in the central nervous system. IP3K-A binds to F-actin in an activity-dependent manner and accumulates in dendritic spines, where it is involved in the regulation of synaptic plasticity. IP3K-A knockout mice exhibit deficits in some forms of hippocampus-dependent learning and synaptic plasticity, such as long-term potentiation in the dentate gyrus synapses of the hippocampus...
2018: PloS One
https://www.readbyqxmd.com/read/29616445/voluntary-exercise-during-adolescence-mitigated-negative-the-effects-of-maternal-separation-stress-on-the-depressive-like-behaviors-of-adult-male-rats-role-of-nmda-receptors
#7
Forouzan Fattahi Masrour, Maghsoud Peeri, Mohammad Ali Azarbayjani, Mir-Jamal Hosseini
Evidence indicates that experiencing early-life stress (ELS) is a risk factor for the development of mental disorders such as depression. Maternal separation stress (MS) is a valid animal model of ELS that caused to induce long-lasting effects on the brain and behaviors of animals. It hypothesized that adolescence is a critical stage in which the brain is still developing, and applying (non)pharmacological therapies in this period may attenuate the effects of ELS on the brain and behavior. Male rats were subjected to MS from postnatal day (PND) 2-14, and the stressed animals were then treated with (1) chronic fluoxetine (FLX) (5 mg/kg) and (2) voluntary running wheel exercise (RW) from PND 30, for 30 days...
April 3, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29616397/adenosine-augmentation-evoked-by-an-ent1-inhibitor-improves-memory-impairment-and-neuronal-plasticity-in-the-app-ps1-mouse-model-of-alzheimer-s-disease
#8
Chia-Chia Lee, Ching-Pang Chang, Chun-Jung Lin, Hsing-Lin Lai, Yu-Han Kao, Sin-Jhong Cheng, Hui-Mei Chen, Yu-Ping Liao, Emilie Faivre, Luc Buée, David Blum, Jim-Min Fang, Yijuang Chern
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and synaptic dysfunction. Adenosine is an important homeostatic modulator that controls the bioenergetic network in the brain through regulating receptor-evoked signaling pathways, bioenergetic machineries, and epigenetic-mediated gene regulation. Equilibrative nucleoside transporter 1 (ENT1) is a major adenosine transporter that recycles adenosine from the extracellular space. In the present study, we report that a small adenosine analogue (designated J4) that inhibited ENT1 prevented the decline in spatial memory in an AD mouse model (APP/PS1)...
April 4, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29604542/design-synthesis-and-bioevaluation-of-1-2-3-9-tetrahydropyrrolo-2-1-b-quinazoline-1-carboxylic-acid-derivatives-as-potent-neuroprotective-agents
#9
Linkui Zhang, Ying Zhao, Jian Wang, Donglin Yang, Chenwen Zhao, Changli Wang, Chao Ma, Maosheng Cheng
Diverse of 1,2,3,9-tetrahydropyrrolo[2,1-b]quinazoline-1-carboxylic acid derivatives were designed, synthesized and evaluated for their neuroprotective activity against NMDA-induced cytotoxicity in vitro, and 5q exhibited excellent neuroprotective activity. The compound 5q was selected for further investigation. We found that 5q could attenuate Ca2+ influx induced by NMDA, meanwhile, 5q could suppress the NR2B up-regulation and increase p-ERK1/2 expression. The molecular docking results showed that 5q might fit well in the binding pocket of 4 and interact with some key residues in the binding pocket of 1 simultaneously...
March 23, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29577884/regional-specific-effects-of-cerebral-ischemia-reperfusion-and-dehydroepiandrosterone-on-synaptic-nmdar-psd-95-complex-in-male-wistar-rats
#10
Marina Zaric, Dunja Drakulic, Ivana Gusevac Stojanovic, Natasa Mitrovic, Ivana Grkovic, Jelena Martinovic
Excessive glutamate efflux and N-methyl-D-aspartate receptor (NMDAR) over-activation represent well-known hallmarks of cerebral ischemia/reperfusion (I/R) injury, still, expression of proteins involved in this aspect of I/R pathophysiology show inconsistent data. Neurosteroid dehydroepiandrosterone (DHEA) has been proposed as potent NMDAR modulator, but its influence on I/R-induced changes up to date remains questionable. Therefore, I/R-governed alteration of vesicular glutamate transporter 1 (vGluT1), synaptic NMDAR subunit composition, postsynaptic density protein 95 (PSD-95) and neuronal morphology alone or following DHEA treatment were examined...
March 22, 2018: Brain Research
https://www.readbyqxmd.com/read/29547750/alterations-in-glutamatergic-signaling-contribute-to-the-decline-of-circadian-photoentrainment-in-aged-mice
#11
Stephany M Biello, David R Bonsall, Lynsey A Atkinson, Penny C Molyneux, Mary E Harrington, Gurprit S Lall
Robust physiological circadian rhythms form an integral part of well-being. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioral activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN)...
February 20, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29513122/treatment-of-secondary-brain-injury-by-perturbing-postsynaptic-density-protein-95-nmda-receptor-interaction-after-intracerebral-hemorrhage-in-rats
#12
Zhifeng Wang, Zhouqing Chen, Junjie Yang, Ziying Yang, Jia Yin, Xiaochun Duan, Haitao Shen, Haiying Li, Zhong Wang, Gang Chen
Postsynaptic density protein-95 (PSD95) plays important roles in the formation, differentiation, remodeling, and maturation of neuronal synapses. This study is to estimate the potential role of PSD95 in cognitive dysfunction and synaptic injury following intracerebral hemorrhage (ICH). The interaction between PSD95 and NMDA receptor subunit NR2B-neurotransmitter nitric oxide synthase (nNOS) could form a signal protein complex mediating excitatory signaling. Besides NR2B-nNOS, PSD95 also can bind to neurexin-1-neuroligin-1 to form a complex and participates in maintaining synaptic function...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29510187/rhynchophylline-suppresses-soluble-a%C3%AE-1-42-induced-impairment-of-spatial-cognition-function-via-inhibiting-excessive-activation-of-extrasynaptic-nr2b-containing-nmda-receptors
#13
Yang Yang, Wei-Gang Ji, Zhi-Ru Zhu, Yu-Ling Wu, Zhi-Yang Zhang, Shao-Chen Qu
Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. The overproduction of soluble amyloid β protein (Aβ) oligomers in the hippocampus is closely involved in impairments in cognitive function at the early stage of Alzheimer's disease (AD). Growing evidences show that RIN possesses neuroprotective effects against Aβ-induced neurotoxicity. However, whether RIN can prevent soluble Aβ1-42 -induced impairments in spatial cognitive function and synaptic plasticity is still unclear...
March 3, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29497125/critical-role-of-sigma-1-receptors-in-central-neuropathic-pain-related-behaviours-after-mild-spinal-cord-injury-in-mice
#14
Sílvia Castany, Georgia Gris, José Miguel Vela, Enrique Verdú, Pere Boadas-Vaello
Sigma-1 receptor (σ1 R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) - a model of central neuropathic pain. The modulatory effect of σ1 R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed...
March 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29481317/a-postmortem-analysis-of-nmda-ionotropic-and-group-1-metabotropic-glutamate-receptors-in-the-nucleus-accumbens-in-schizophrenia
#15
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)...
March 2018: Journal of Psychiatry & Neuroscience: JPN
https://www.readbyqxmd.com/read/29476874/glutamate-dependent-regulation-of-food-intake-is-altered-with-age-through-changes-in-nmda-receptor-phenotypes-on-vagal-afferent-neurons
#16
Dulce M Minaya, Rachel Wanty Larson, Piotr Podlasz, Krzysztof Czaja
Compared to younger individuals, older human subjects have significantly lower food intakes and an increased satiety response. N-methyl-d-aspartate (NMDA) receptors expressed by vagal afferent neurons originating from nodose ganglia (NG) are involved in modulating the satiety response. The present study investigated how NMDA receptor subunit phenotypes in NG neurons change with age and how these age-related alterations in food intake are modulated by presynaptic NMDA receptors in the NG of male Sprague Dawley rats (six week-old and sixty week-old)...
May 15, 2018: Physiology & Behavior
https://www.readbyqxmd.com/read/29465478/glutamatergic-modulators-in-depression
#17
Ioline D Henter, Rafael Teixeira de Sousa, Carlos A Zarate
Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies...
February 20, 2018: Harvard Review of Psychiatry
https://www.readbyqxmd.com/read/29464191/impact-of-nmda-receptor-overexpression-on-cerebellar-purkinje-cell-activity-and-motor-learning
#18
Elisa Galliano, Martijn Schonewille, Saša Peter, Mandy Rutteman, Simone Houtman, Dick Jaarsma, Freek E Hoebeek, Chris I De Zeeuw
In many brain regions involved in learning NMDA receptors (NMDARs) act as coincidence detectors of pre- and postsynaptic activity, mediating Hebbian plasticity. Intriguingly, the parallel fiber (PF) to Purkinje cell (PC) input in the cerebellar cortex, which is critical for procedural learning, shows virtually no postsynaptic NMDARs. Why is this? Here, we address this question by generating and testing independent transgenic lines that overexpress NMDAR containing the type 2B subunit (NR2B) specifically in PCs...
January 2018: ENeuro
https://www.readbyqxmd.com/read/29463009/docosahexaenoic-acid-helps-to-lessen-extinction-memory-in-rats
#19
Michio Hashimoto, Shahdat Hossain, Masanori Katakura, Abdullah Al Mamun, Osamu Shido
Abstract : Memory extinction is referred to as a learning process in which a conditioned response (CR) progressively reduces over time as an animal learns to uncouple a response from a stimulus. Extinction occurs when the rat is placed into a context without shock after training. Docosahexaenoic acid (DHA, C22:6, n-3) is implicated in memory formation in mammalian brains. In a two-way active shuttle-avoidance apparatus, we examined whether DHA affects the extinction memory and the expression of brain cognition-related proteins, including gastrin-releasing peptide receptor (GRPR), brain-derived neurotrophic factor receptor (BDNFR) tyrosine kinase receptor B (TrKB), and N-methyl-d-aspartate receptor (NMDAR) subunits NR2A and NR2B...
February 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29461008/propofol-exposure-during-early-gestation-impairs-learning-and-memory-in-rat-offspring-by-inhibiting-the-acetylation-of-histone
#20
Jiamei Lin, Shengqiang Wang, Yunlin Feng, Weihong Zhao, Weilu Zhao, Foquan Luo, Namin Feng
Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30...
May 2018: Journal of Cellular and Molecular Medicine
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