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https://www.readbyqxmd.com/read/29763633/estradiol-induced-enhancement-of-fear-extinction-in-female-rats-the-role-of-nmda-receptor-activation
#1
Bronwyn M Graham, Elliot Scott
Converging cross-species evidence indicates that fear extinction (the laboratory basis of exposure therapy for anxiety disorders) in females is modulated by endogenous and exogenous estradiol. The mechanisms underlying estradiol's influences on fear extinction are largely undefined. However, one likely candidate is the NMDA-receptor (NMDAr), activation of which is necessary for estradiol-mediated enhancements in structural and functional neural plasticity, as well as extinction consolidation in males. Here, we demonstrate that systemic co-administration of the non-competitive NMDAr antagonist, MK801, blocked the enhancement of fear extinction by systemic estradiol in ovariectomized rats...
May 12, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29749444/effects-of-intravenous-anesthetics-on-the-phosphorylation-of-camp-response-element%C3%A2-binding-protein-in-hippocampal-slices-of-adult-mice
#2
Haiying Gao, Lingyu Zhang, Zhenyi Chen, Shuncui Liu, Qinghong Zhang, Bingxi Zhang
cAMP response‑element binding protein (CREB) functions in hippocampal synaptic plasticity and memory formation. However, it remains unknown whether intravenous anesthetics modulate CREB. The present study aimed to examine the effects of intravenous anesthetics on CREB phosphorylation in the mouse hippocampus. CREB phosphorylation was examined in hippocampal slices with and without pharmacological or intravenous anesthetics via immunoblotting. In a dose‑response experiment, the concentrations of intravenous anesthetics ranged from 10‑9 to 10‑4 mol/l for 1 h...
April 27, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29725295/differential-hyperphosphorylation-of-tau-s199-t231-and-s396-in-organotypic-brain-slices-of-alzheimer-mice-a-model-to-study-early-tau-hyperphosphorylation-using-okadaic-acid
#3
Bettina M Foidl, Christian Humpel
Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the brain, characterized by extracellular aggregation of beta-amyloid (Aβ) and hyperphosphorylation of tau causing intraneuronal neurofibrillary tangles (NFTs). There is urgent need to study the interactions between Aβ and tau, especially to solve the question of the pathological cascade. In the present study, we aim to develop a model of organotypic brain slices in which both plaque and tau pathology can be examined. Organotypic brain slices (150 μm thick, coronal, at the hippocampal level) from adult (9 month) wildtype (WT, C57BL/6N) and transgenic AD mice (TG, APP_SweDI) were cultured for 2 weeks...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29706890/simvastatin-enhances-activity-and-trafficking-of-%C3%AE-7-nicotinic-acetylcholine-receptor-in-hippocampal-neurons-through-pkc-and-camkii-signaling-pathways
#4
Tingting Chen, Ya Wang, Tingting Zhang, Baofeng Zhang, Lei Chen, Liandong Zhao, Ling Chen
Simvastatin (SV) enhances glutamate release and synaptic plasticity in hippocampal CA1 region upon activation of α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we examined the effects of SV on the functional activity of α7nAChR on CA1 pyramidal cells using patch-clamp recording and explored the underlying mechanisms. We found that the treatment of hippocampal slices with SV for 2 h induced a dose-dependent increase in the amplitude of ACh-evoked inward currents ( I ACh ) and the level of α7nAChR protein on the cell membrane without change in the level of α7nAChR phosphorylation...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29700292/enhancement-of-5-ht-2a-receptor-function-and-blockade-of-kv1-5-by-mk801-and-ketamine-implications-for-pcp-derivative-induced-disease-models
#5
Haiyue Lin, Jae Gon Kim, Sang Woong Park, Hyun Ju Noh, Jeong Min Kim, Chang Yong Yoon, Nam-Sik Woo, Bokyung Kim, Sung Il Cho, Bok Hee Choi, Dong Jun Sung, Young Min Bae
MK801 and ketamine, which are phencyclidine (PCP) derivative N-methyl-d-aspartate receptor (NMDAr) blockers, reportedly enhance the function of 5-hydroxytryptamine (HT)-2A receptors (5-HT2A Rs). Both are believed to directly affect the pathogenesis of schizophrenia, as well as hypertension. 5-HT2A R signaling involves the inhibition of Kv conductance. This study investigated the interaction of these drugs with Kv1.5, which plays important roles in 5-HT2A R signaling and in regulating the excitability of the cardiovascular and nervous system, and the potential role of this interaction in the enhancement of the 5-HT2A R-mediated response...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29689373/effects-of-the-nmda-receptor-antagonists-dizocilpine-and-ro-63-1908-on-delay-discounting-and-risky-decision-making-in-a-gambling-task
#6
Guy A Higgins, Leo B Silenieks, Cam MacMillan, Fiona D Zeeb, Sandy Thevarkunnel
Previous studies demonstrated that NMDA receptor antagonists such as dizocilpine (MK801) and the GluN2B NMDA antagonist Ro 63-1908 promote impulsive action (motor impulsivity). The effects of these treatments on impulsive choice and decision-making is less well characterized. Two experiments were undertaken. In the first experiment, given evidence for delay order as a factor in choice selection, the effect of dizocilpine was examined in a delay discounting task with separate groups of male Long-Evans rats trained to a schedule of either ascending (i...
April 21, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29667304/inhibition-of-alpha7-nicotinic-receptors-in-the-ventral-hippocampus-selectively-attenuates-reinstatement-of-morphine-conditioned-place-preference-and-associated-changes-in-ampa-receptor-binding
#7
Victoria L Wright, Polymnia Georgiou, Alexis Bailey, David J Heal, Christopher P Bailey, Susan Wonnacott
Recurrent relapse is a major problem in treating opiate addiction. Pavlovian conditioning plays a role in recurrent relapse whereby exposure to cues learned during drug intake can precipitate relapse to drug taking. α7 nicotinic acetylcholine receptors (nAChRs) have been implicated in attentional aspects of cognition and mechanisms of learning and memory. In this study we have investigated the role of α7 nAChRs in morphine-conditioned place preference (morphine-CPP). CPP provides a model of associative learning that is pertinent to associative aspects of drug dependence...
April 17, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29578035/ras-inhibitor-s-trans-trans-farnesylthiosalicylic-acid-enhances-spatial-memory-and-hippocampal-long-term-potentiation-via-up-regulation-of-nmda-receptor
#8
Ya Wang, Tingting Chen, Zihao Yuan, Yajie Zhang, Baofeng Zhang, Liandong Zhao, Ling Chen
Statins by reducing farnesyl-pyrophosphate or farnesyl transferase inhibitors have been demonstrated to enhance spatial memory and long-term potentiation (LTP). The objective of this study was to investigate effects of the synthetic Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS) on spatial cognitive function in adult mice, synaptic plasticity in hippocampal CA1 regions, and NMDA receptor (NMDAr) activity of pyramidal cells. Here, we show that administering FTS (5 mg/kg, i.p.) enhanced spatial cognitive performance, as assessed via Morris water maze and Y-maze tests...
March 22, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29545387/elucidating-the-mechanisms-of-fear-extinction-in-developing-animals-a-special-case-of-nmda-receptor-independent-extinction-in-adolescent-rats
#9
Madelyne A Bisby, Kathryn D Baker, Rick Richardson
NMDA receptors (NMDARs) are considered critical for the consolidation of extinction but recent work challenges this assumption. Namely, NMDARs are not required for extinction retention in infant rats as well as when extinction training occurs for a second time (i.e., reextinction) in adult rats. In this study, a possible third instance of NMDAR-independent extinction was tested. Although adolescents typically exhibit impaired extinction retention, rats that are conditioned as juveniles and then given extinction training as adolescents (JuvCond-AdolesExt) have good extinction retention...
April 2018: Learning & Memory
https://www.readbyqxmd.com/read/29523414/presynaptic-effects-of-n-methyl-d-aspartate-receptors-enhance-parvalbumin-cell-mediated-inhibition-of-pyramidal-cells-in-mouse-prefrontal-cortex
#10
Diego E Pafundo, Takeaki Miyamae, David A Lewis, Guillermo Gonzalez-Burgos
BACKGROUND: Testing hypotheses regarding the role of N-methyl-D-aspartate receptor (NMDAR) hypofunction in schizophrenia requires understanding the mechanisms of NMDAR regulation of prefrontal cortex (PFC) circuit function. NMDAR antagonists are thought to produce pyramidal cell (PC) disinhibition. However, inhibitory parvalbumin-positive basket cells (PVBCs) have modest NMDAR-mediated excitatory drive and thus are unlikely to participate in NMDAR antagonist-mediated disinhibition. Interestingly, recent studies demonstrated that presynaptic NMDARs enhance transmitter release at central synapses...
January 31, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29486970/bicyclo-aryl-methyl-benzamides-as-inhibitors-of-glyt1
#11
Jeffrey G Varnes, Hui Xiong, Janet M Forst, Christopher R Holmquist, Glen E Ernst, William Frietze, Bruce Dembofsky, Don W Andisik, William E Palmer, Lindsay Hinkley, Gary B Steelman, Deidre E Wilkins, Gaochao Tian, Gerald Jonak, William M Potts, Xia Wang, Todd A Brugel, Cristóbal Alhambra, Michael W Wood, Chris A Veale, Jeffrey S Albert
A series of isoquinuclidine benzamides as glycine uptake inhibitors for the treatment of schizophrenia are described. Potency, lipophilicity, and intrinsic human microsomal clearance were parameters for optimization. Potency correlated with the nature of the ortho substituents of the benzamide ring, and reductions in lipophilicity could be achieved through heteroatom incorporation in the benzamide and pendant phenyl moieties. Improvements in human CLint were achieved through changes in ring size and the N-alkyl group of the isoquinuclidine itself, with des-alkyl derivatives (40-41, 44) demonstrating the most robust microsomal stability...
April 1, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29483860/the-histamine-h3-receptor-antagonist-dl77-ameliorates-mk801-induced-memory-deficits-in-rats
#12
Nermin Eissa, Nadia Khan, Shreesh K Ojha, Dorota Łazewska, Katarzyna Kieć-Kononowicz, Bassem Sadek
The role of Histamine H3 receptors (H3Rs) in memory, and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer disease (AD) is well-accepted. For that reason, the procognitive effects of the H3R antagonist DL77 on cognitive impairments induced with MK801 were tested in an inhibitory passive avoidance paradigm (PAP) and novel object recognition (NOR) task in adult male rats, using donepezil (DOZ) as a standard drug. Acute systemic pretreatment with DL77 (2...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29468822/phycoerythrin-derived-tryptic-peptide-of-a-red-alga-pyropia-yezoensis-attenuates-glutamate-induced-er-stress-and-neuronal-senescence-in-primary-rat-hippocampal-neurons
#13
Jeong Hwan Oh, Eun-Young Kim, Taek-Jeong Nam
SCOPE: Glutamate excitotoxicity has been observed in association with neurodegenerative disorders. This study aimed to investigate whether a phycoerythrin-derived tryptic peptide of Pyropia yezoensis (PYP) reduces glutamate-induced excitotoxicity and neuronal senescence in primary rat hippocampal neurons. METHODS AND RESULTS: Glutamate exposure (100 μm) decreased cell viability and increased expression of endoplasmic reticulum (ER) stress response protein glucose-regulated protein 78 (GRP78) starting at 60 min following glutamate exposure, which was prevented by pretreating the neurons with PYP (1 μg mL-1 )...
April 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29463705/controlling-of-glutamate-release-by-neuregulin3-via-inhibiting-the-assembly-of-the-snare-complex
#14
Ya-Nan Wang, Dwight Figueiredo, Xiang-Dong Sun, Zhao-Qi Dong, Wen-Bing Chen, Wan-Peng Cui, Fang Liu, Hong-Sheng Wang, Hai-Wen Li, Heath Robinson, Er-Kang Fei, Bing-Xing Pan, Bao-Ming Li, Wen-Cheng Xiong, Lin Mei
Neuregulin3 (NRG3) is a growth factor of the neuregulin (NRG) family and a risk gene of various severe mental illnesses including schizophrenia, bipolar disorders, and major depression. However, the physiological function of NRG3 remains poorly understood. Here we show that loss of Nrg3 in GFAP-Nrg3 f/f mice increased glutamatergic transmission, but had no effect on GABAergic transmission. These phenotypes were observed in Nex-Nrg3 f/f mice, where Nrg3 was specifically knocked out in pyramidal neurons, indicating that Nrg3 regulates glutamatergic transmission by a cell-autonomous mechanism...
March 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29438741/different-mechanisms-underlie-stress-induced-changes-in-plasticity-and-metaplasticity-in-the-prefrontal-cortex-of-juvenile-and-adult-animals-emotional-induced-metaplasticity-in-the-prefrontal-cortex
#15
Tala Khazen, Kuldeep Shrivastava, Reem Jada, Ossama A Hatoum, Mouna Maroun
Metaplasticity is the dynamic regulation of the ability to induce activity-dependent synaptic plasticity and is governed by the prior history of the synapses. Previous reports by others and us have shown that behavioral stress induces a form of emotional metaplasticity that affects the ability to induce LTP in the subiculum-medial prefrontal cortex pathway, which depends on NMDA receptors (NMDAr). However, studies addressing the effects of stress on LTP and metaplasticity have mainly focused on the adult animal...
February 10, 2018: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29325386/-the-protective-effect-of-the-activation-of-nmdar1-erk1-2-signal-pathway-induced-by-levodopa-on-visual-cortical-neurons-in-monocular-deprivation-rats
#16
X N Sun, H L Wang, G Qiao, J Tao, C Liu, X H Hao
Objective: To investigate the protection effects of the activation of NMDAR1(NMDA receptor 1)/ERK1/2 signal pathway on visual cortex nerve cells induced by levodopa in amblyopia rats. Methods: SD rats of SPF grade, were randomly divided into for groups of 9, group A. Control, B. MD group, C. L-levodopa(20 mg·kg(-1))+MD group, D. H-levodopa (80 mg·kg(-1))+MD group, E. H-levodopa+MD+MK801 group, F. H-levodopa+MD+PD98059 group, G. MD+MK801 group, H. MD+PD98059 group, I. MD+DMSO group. Amblyopia rats were made by suture of the right eye...
December 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29315577/bidirectional-variation-in-glutamate-efflux-in-the-medial-prefrontal-cortex-induced-by-selective-positive-and-negative-allosteric-mglur5-modulators
#17
Sarah N Isherwood, Trevor W Robbins, Jeffrey W Dalley, Anton Pekcec
Dysregulation of prefrontal cortical glutamatergic signalling via NMDA receptor hypofunction has been implicated in cognitive dysfunction and impaired inhibitory control in such neuropsychiatric disorders as schizophrenia, attention-deficit hyperactivity disorder and drug addiction. Although NMDA receptors functionally interact with metabotropic glutamate receptor 5 (mGluR5), the consequence of this interaction for glutamate release in the prefrontal cortex (PFC) remains unknown. We therefore investigated the effects of positive and negative allosteric mGluR5 modulation on changes in extracellular glutamate efflux in the medial PFC (mPFC) induced by systemic administration of the non-competitive NMDA receptor antagonist dizocilpine (or MK801) in rats...
January 6, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29249806/cortical-high-gamma-network-oscillations-and-connectivity-a-translational-index-for-antipsychotics-to-normalize-aberrant-neurophysiological-activity
#18
A Ahnaou, H Huysmans, T Van de Casteele, W H I M Drinkenburg
Oscillatory activity in the gamma frequency range is a critical mechanism, which integrates neural networks within and across brain structures during cognitive processes. In schizophrenia, abnormalities in high gamma oscillations are ubiquitous and most likely reflect dysfunction in neuronal networks. In conscious rats, disturbed network oscillations associated with positive symptoms and cognitive deficits were modeled in different cortical areas by the dopaminergic agonist (amphetamine) and the N-methyl-D-aspartate (NMDA) receptor antagonists (PCP and MK801)...
December 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29241309/involvement-of-endothelial-nitric-oxide-synthase-activation-in-midkine-mediated-central-hypotensive-effects
#19
Ching-Huang Lin, Jun-Yen Pan, Jung-Jui Chang, Hsin-Hung Chen, Pei-Wen Cheng, Ching-Jiunn Tseng
The growth factor midkine (MK) has been implicated in various biologic and pathologic events. It has been shown that the peripheral influence of MK on cardiovascular regulation is due to an influence on the renin-angiotensin system (RAS). The nucleus tractus solitarii (NTS) is the primary integrative center for cardiovascular control and other autonomic functions in the central nervous system. However, the signaling mechanisms involved in MK-mediated cardiovascular effects in the NTS remain unclear. In this study, we investigated whether the RAS and/or N-methyl-D-aspartate (NMDA) receptor-calmodulin-endothelial nitric oxide synthase (eNOS) signaling pathways were both involved in MK-mediated blood pressure (BP) regulation in the NTS of Wistar-Kyoto (WKY) rats...
December 31, 2017: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/29200911/dual-control-of-the-vestibulosympathetic-reflex-following-hypotension-in-rats
#20
Sang Eon Park, Yuan-Zhe Jin, Byung Rim Park
Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP...
November 2017: Korean Journal of Physiology & Pharmacology
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