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https://www.readbyqxmd.com/read/28902407/trpc6-expression-in-neurons-is-differentially-regulated-by-nr2a-and-nr2b-containing-nmda-receptors
#1
Zhongwei Qu, Yuqing Wang, Xia Li, Lin Wu, Yizheng Wang
The expression of transient receptor potential canonical 6 (TRPC6) in central nervous system (CNS) is important for neuronal functions and certain neural disorders. However, the regulatory mechanism of TRPC6 expression in neurons is still obscure. In the current study, we show that TRPC6 expression in the primary cultured cortical neurons is bidirectionally regulated by glutamate. Activation of NR2A-containing NMDARs induces TRPC6 transcription through a calcineurin-dependent pathway. In contrast, activation of NR2B-containing NMDARs causes TRPC6 degradation through calpain...
September 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28890075/down-regulation-of-dorsal-striatal-%C3%AE-camkii-causes-striatum-related-cognitive-and-synaptic-disorders
#2
Qi Wang, Pengcheng Yin, Bin Yu, Zheng Zhao, Gal Richter-Levin, Lu Yu, Xiaohua Cao
Alpha calcium/calmodulin dependent protein kinase II (αCaMKII) is a serine/threonine protein kinase which is expressed abundantly in dorsal striatum and is highly involved in the corticostriatal synaptic plasticity. Nevertheless, it currently remains unclear whether and how αCaMKII plays a in the striatum-related neural disorders. To address the above issue, lentivirus-mediated short hairpin RNA (shRNA) was used to silence the expression of αCaMKII gene in the dorsal striatum of mice. As a consequence of down-regulation of dorsal striatal αCaMKII expression, we observed defective motor skill learning in accelerating rotarod and response learning in water cross maze...
September 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28882411/prenatal-stress-induced-impairments-of-cognitive-flexibility-and-bidirectional-synaptic-plasticity-are-possibly-associated-with-autophagy-in-adolescent-male-offspring
#3
Hui Zhang, Yingchun Shang, Xi Xiao, Mei Yu, Tao Zhang
Prenatal stress (PS) brings numerous outcomes on offspring, including anxiety, depression-like behavior and other cognitive disorder. In this study, a rat model of PS was established by using restraint stress for 45min three times per day from the 15th to 21st day of pregnancy. Behavioral tests, including open field test (OPT), elevated plus-maze (EPM) and Morris water-maze (MWM), were performed in adolescent male-offspring. The bidirectional synaptic plasticity, including long-term potential (LTP) and depotentiation (DEP), from the hippocampal Schaffer collaterals to CA1 region was subsequently measured...
September 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28873095/longistyline-c-acts-antidepressant-in-vivo-and-neuroprotection-in-vitro-against-glutamate-induced-cytotoxicity-by-regulating-nmdar-nr2b-erk-pathway-in-pc12-cells
#4
Yamin Liu, Ning Zhao, Chenchen Li, Qi Chang, Xinmin Liu, Yonghong Liao, Ruile Pan
Depressive disorder is a common psychiatric disease which ranks among the leading cause of disability worldwide. The antidepressants presently used had low cure rate and caused a variety of side-effects. The screening of antidepressant drugs is usually used classic behavioural tests and neuroprotective strategy. Longistyline C, a natural stilbene isolated from the leaves of Cajanuscajan (L.) Millsp, was firstly investigated the antidepressant effect using animal behavioural tests, and studied the neuroprotection and its possible signaling pathways on glutamate-induced injury in PC12 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28866028/long-term-impairment-of-cognitive-functions-and-alterations-of-nmdar-subunits-after-continuous-microwave-exposure
#5
Hui Wang, Shengzhi Tan, Xinping Xu, Li Zhao, Jing Zhang, Binwei Yao, Yabing Gao, Hongmei Zhou, Ruiyun Peng
OBJECTIVE: The long term effects of continuous microwave exposure cannot be ignored for the simulation of the real environment and increasing concerns about the negative cognitive effects of microwave exposure. METHODS: In this study, 220 male Wistar rats were exposed by a 2.856GHz radiation source with the average power density of 0, 2.5, 5 and 10mW/cm(2) for 6min/day, 5days/week and up to 6weeks. The MWM task, the EEG analysis, the hippocampus structure observation and the western blot were applied until the 12months after microwave exposure to detect the spatial learning and memory abilities, the cortical electrical activity, changes of hippocampal structure and the NMDAR subunits expressions...
September 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28865018/making-of-a-synapse-recurrent-roles-of-drebrin-a-at-excitatory-synapses-throughout-life
#6
Chiye Aoki, Ang D Sherpa
Mature excitatory synapses are composed of more than 1500 proteins postsynaptically and hundreds more that operate presynaptically. Among them, drebrin is an F-actin-binding protein that increases noticeably during juvenile synaptogenesis. Electron microscopic analysis reveals that drebrin is highly enriched specifically on the postsynaptic side of excitatory synapses. Since dendritic spines are structures specialized for excitatory synaptic transmission, the function of drebrin was probed by analyzing the ultrastructural characteristics of dendritic spines of animals with genetic deletion of drebrin A (DAKO), the adult isoform of drebrin...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28864206/mice-lacking-hippocampal-left-right-asymmetry-show-non-spatial-learning-deficits
#7
Akihiro Shimbo, Yutaka Kosaki, Isao Ito, Shigeru Watanabe
Left-right asymmetry is known to exist at several anatomical levels in the brain and recent studies have provided further evidence to show that it also exists at a molecular level in the hippocampal CA3-CA1 circuit. The distribution of N-methyl-d-aspartate (NMDA) receptor NR2B subunits in the apical and basal synapses of CA1 pyramidal neurons is asymmetrical if the input arrives from the left or right CA3 pyramidal neurons. In the present study, we examined the role of hippocampal asymmetry in cognitive function using β2-microglobulin knock-out (β2m KO) mice, which lack hippocampal asymmetry...
August 31, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28858643/exploring-putative-inhibitors-of-death-associated-protein-kinase-1-dapk1-via-targeting-gly-glu-leu-gel-and-pro-glu-asn-pen-substrate-recognition-motifs
#8
Pratibha Singh, Priti Talwar
Recently, a new signaling complex Death Associated Protein Kinase 1 (DAPK1) ̶ N-methyl-D-aspartate receptor subtype 2B (NMDAR2B or NR2B) engaged in the neuronal death cascade was identified and it was found that after stroke injury, N-methyl-D-aspartate glutamate (NMDA) receptors interact with DAPK1 through NR2B subunit and lead to excitotoxicity via over-activation of NMDA receptors. An acute brain injury, such as stroke, is a serious life-threatening medical condition which occurs due to poor blood supply to the brain and further leads to neuronal cell death...
August 18, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28854243/antiparkinsonian-effects-of-the-radiprodil-and-tozadenant-combination-in-mptp-treated-marmosets
#9
Anne Michel, Jean-Marie Nicolas, Sarah Rose, Michael Jackson, Peter Colman, Willy Briône, David Sciberras, Pierandrea Muglia, Dieter K Scheller, Martin Citron, Patrick Downey
OBJECTIVE: Investigate a combination of two clinically tested drugs, the NR2B antagonist Radiprodil and the A2A antagonist Tozadenant in the MPTP-treated marmoset model of Parkinson's Disease (PD). BACKGROUND: In PD, there remains a need for the development of non-dopaminergic drugs to effectively treat the motor symptoms without the induction of L-Dopa-induced motor complications. METHODS: Clinically relevant doses of Radiprodil and Tozadenant were given both alone and in combination without the addition of L-Dopa, and the antiparkinsonian efficacy of the treatments was assessed in a primate model of PD...
2017: PloS One
https://www.readbyqxmd.com/read/28840468/the-kinase-fyn-as-a-novel-intermediate-in-l-dopa-induced-dyskinesia-in-parkinson-s-disease
#10
Sara Sanz-Blasco, Melina P Bordone, Ana Damianich, Gimena Gomez, M Alejandra Bernardi, Luciana Isaja, Irene R Taravini, Diane P Hanger, M Elena Avale, Oscar S Gershanik, Juan E Ferrario
Dopamine replacement therapy with L-DOPA is the treatment of choice for Parkinson's disease; however, its long-term use is frequently associated with L-DOPA-induced dyskinesia (LID). Many molecules have been implicated in the development of LID, and several of these have been proposed as potential therapeutic targets. However, to date, none of these molecules have demonstrated full clinical efficacy, either because they lie downstream of dopaminergic signaling, or due to adverse side effects. Therefore, discovering new strategies to reduce LID in Parkinson's disease remains a major challenge...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28837653/computational-investigation-of-amyloid-%C3%AE-induced-location-and-subunit-specific-disturbances-of-nmdar-at-hippocampal-dendritic-spine-in-alzheimer-s-disease
#11
Jingyi Liang, Don Kulasiri, Sandhya Samarasinghe
In Alzheimer's disease (AD), dysregulation of intracellular Ca2+ signalling has been observed as an early event prior to the presence of clinical symptoms and is believed to be a crucial factor contributing to AD pathogenesis. Amyloid-β oligomers (AβOs) disturb the N-methyl-D-aspartate receptor (NMDAR)-mediated postsynaptic Ca2+ signalling in response to presynaptic stimulation by increasing the availability of extracellular glutamate as well as directly disturbing the NMDARs. The abnormal Ca2+ response can further lead to impairments in long-term potentiation (LTP), an important process in memory formation...
2017: PloS One
https://www.readbyqxmd.com/read/28807933/mice-deficient-in-lysophosphatidic-acid-acyltransferase-%C3%AE-lpaat%C3%AE-acylglycerophosphate-acyltransferase-4-agpat4-have-impairments-in-spatial-learning-and-memory-associated-with-reductions-in-nmda-and-ampa-receptors
#12
Ryan M Bradley, Emily B Mardian, Darin Bloemberg, Juan J Aristizabal Henao, Andrew S Mitchell, Phillip M Marvyn, Katherine A Moes, Ken D Stark, Joe Quadrilatero, Robin E Duncan
We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here we report that Lpaatδ (-/-) mice display impaired spatial learning and memory compared to wildtype littermates in the Morris Water Maze, and investigated potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged...
August 14, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28804711/annotation-of-the-nuclear-receptors-in-an-estuarine-fish-species-fundulus-heteroclitus
#13
William S Baldwin, W Tyler Boswell, Gautam Ginjupalli, Elizabeth J Litoff
The nuclear receptors (NRs) are ligand-dependent transcription factors that respond to various internal as well as external cues such as nutrients, pheromones, and steroid hormones that play crucial roles in regulation and maintenance of homeostasis and orchestrating the physiological and stress responses of an organism. We annotated the Fundulus heteroclitus (mummichog; Atlantic killifish) nuclear receptors. Mummichog are a non-migratory, estuarine fish with a limited home range often used in environmental research as a field model for studying ecological and evolutionary responses to variable environmental conditions such as salinity, oxygen, temperature, pH, and toxic compounds because of their hardiness...
2017: Nuclear Receptor Research
https://www.readbyqxmd.com/read/28790892/a-critical-period-for-the-rapid-modification-of-synaptic-properties-at-the-vpm-relay-synapse
#14
Libiao Pan, Junhua Yang, Qian Yang, Xiaomeng Wang, Liya Zhu, Yali Liu, Huifang Lou, Chou Xu, Ying Shen, Hao Wang
In addition to cortical areas, the thalamus also displays plasticity during a critical period in early life. Since most sensory information is transmitted to the cortex via the thalamus, it will be of significant interest to understand the precise time window and underlying mechanisms of this critical period in the thalamus. By using in vitro whole-cell patch recording in acute brain slices, we found that VPm relay synapses were only sensitive to whisker deprivation from postnatal day 11 (P11) to P14. Whisker deprivation initiated within the P11 to P14 window significantly reduced the amplitude of AMPAR-EPSCs, but not NMDAR-EPSCs when recorded 24 h after whisker removal...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28790021/deficient-striatal-adaptation-in-aminergic-and-glutamatergic-neurotransmission-is-associated-with-tardive-dyskinesia-in-non-human-primates-exposed-to-antipsychotic-drugs
#15
Catherine Lévesque, Giovanni Hernandez, Souha Mahmoudi, Frédéric Calon, Fabrizio Gasparini, Baltazar Gomez-Mancilla, Pierre J Blanchet, Daniel Lévesque
Tardive dyskinesia (TD) is a potentially disabling condition encompassing all delayed, persistent, and often irreversible abnormal involuntary movements arising in a fraction of subjects during long-term exposure to centrally acting dopamine receptor-blocking agents such as antipsychotic drugs and metoclopramide. However, the pathogenesis of TD has proved complex and remains elusive. To investigate the mechanism underlying the development of TD, we have chronically exposed 17 Cebus apella monkeys to typical (11) or atypical (6) antipsychotic drugs...
August 5, 2017: Neuroscience
https://www.readbyqxmd.com/read/28754363/discovery-of-orally-bioavailable-cyclohexanol-based-nr2b-selective-nmda-receptor-antagonists-with-analgesic-activity-utilizing-a-scaffold-hopping-approach
#16
Kosuke Anan, Moriyasu Masui, Shinichiro Hara, Miho Ohara, Masaharu Kume, Shoichi Yamamoto, Shunji Shinohara, Hiroki Tsuji, Shinji Shimada, Shigenori Yagi, Nobuyoshi Hasebe, Hiroyuki Kai
NR2B subunit containing N-methyl-d-aspartate (NMDA) receptor is an attractive target for chronic pain due to its involvement in disease states and its limited distribution in the central nervous system. Cyclohexanol-based leads 6a and 6c were identified as potent NR2B-selective NMDA antagonists utilizing a scaffold hopping approach. Further optimization of this series through replacement of the amide in the leads with an isoxazole and efforts to optimize the pharmacokinetic profiles led to the discovery of orally available brain penetrants 7k and 7l, which demonstrated analgesic activity in the mouse formalin test at early and late phases...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28746067/perturbing-nr2b-psd-95-interaction-relieves-neuropathic-pain-by-inactivating-camkii-creb-signaling
#17
Fangxia Xu, Xin Zhao, Lin Liu, Jia Song, Yingjun Zhu, Shuaishuai Chu, Xueming Shao, Xiuxiu Li, Zhengliang Ma, Xiaoping Gu
Neuropathic pain is characterized by central sensitization. The interaction between N-methyl-D-aspartate receptors (NMDARs) and postsynaptic density protein-95 (PSD-95) plays a major role in central sensitization. Here, we aimed to investigate the analgesic effect of disruption of the interaction between NMDAR and PSD-95. Chronic dorsal root ganglia compression model rats were used to mimic sciatica. Thermal hyperalgesia and mechanical allodynia were evaluated. The expression of spinal phospho-NR2B, PSD-95, calcium/calmodulin-dependent protein kinase II (CaMKII), and cAMP response element binding protein (CREB) was measured using western blotting...
September 6, 2017: Neuroreport
https://www.readbyqxmd.com/read/28745671/-a-role-of-interactions-between-n-methyl-d-aspartate-and-dopamine-receptors-in-facial-emotion-recognition-impairment-in-schizophrenia
#18
M V Alfimova, V E Golimbet, G I Korovaitseva, T V Lezheiko, D V Tikhonov, T K Ganisheva, N B Berezin, A A Snegireva, T K Shemiakina
AIM: To search for genetic mechanisms of facial emotion recognition (FER) impairment, one of the features of schizophrenia that affects social adaptation of patients. Based on the view implicating the interplay between dopaminergic and glutamatergic systems into the pathogenesis of schizophrenia, authors explored the interaction effects of the C366G polymorphism in the GRIN2B gene encoding NMDA receptor subunit NR2B with ANKK1/DRD2 Taq1A and 48-VNTR DRD4 polymorphisms on FER. MATERIAL AND METHODS: GRIN2B -DRD2 interaction effects were studied in a sample of 237 patients and 235 healthy controls, GRIN2B - DRD4 in 268 patients and 208 controls...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28738742/effects-of-erk1-2-kinases-inactivation-on-the-nigrostriatal-system-of-krushinsky-molodkina-rats-genetically-prone-to-audiogenic-seizures
#19
Nadezhda A Dorofeeva, Yuliya S Grigorieva, Liubov S Nikitina, Elena A Lavrova, Elizaveta V Nasluzova, Margarita V Glazova, Elena V Chernigovskaya
Recently, we demonstrated that inhibition of ERK1/2 activity by SL-327 treatment blocks seizure behavior in Krushinsky-Molodkina (KM) rats, which was mediated by altering of GABA and glutamate release mechanism in the hippocampus. Basal ganglia representing various subcortical cell groups play a significant role in the regulation of motor activity, including epileptiform seizures. OBJECTIVES:  To verify if nigrostriatal system could be also affected by SL-327 treatment we analyzed the expression of tyrosine hydroxylase, D1 and D2 dopamine receptors, NR2B subunit of NMDA receptor as well as vesicular glutamate transporter VGLUT2 and glutamic acid decarboxylases GAD65/67 in the striatum and substantia nigra of KM rats...
July 24, 2017: Neurological Research
https://www.readbyqxmd.com/read/28729940/propofol-induced-downregulation-of-nr2b-membrane-translocation-in-hippocampus-and-spatial-memory-deficits-of-neonatal-mice
#20
Yuzhu Wang, Song Han, Ruquan Han, Yue Su, Junfa Li
BACKGROUND: Thousands of infants and children are undergoing anesthesia around the world every day. But impacts of anesthetics on the developing neural system remain unclear yet. Previous evidence showed that anesthesia might affect the developing neural system. Thus, early-life anesthesia becomes a critical issue in clinical pediatric practice. Hence, propofol, a short-acting and widely applied intravenous anesthetic, has been gaining focus upon neonatal anesthesia. METHODS: Fifty-four male C57BL/6J mice were randomly divided into following three groups: group D6 intraperitoneally (i...
July 2017: Brain and Behavior
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