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https://www.readbyqxmd.com/read/29157983/blockade-of-nmda-receptors-blocks-the-acquisition-of-cocaine-conditioned-approach-in-rats
#1
Ewa Galaj, Neal Seepersad, Zena Dakmak, Robert Ranaldi
Conditioned stimuli (CSs) exert motivational effects on both adaptive and pathological reward-related behaviors, including drug taking and seeking. We developed a paradigm that allows us to investigate the neuropharmacology by which previously neutral stimuli acquire the capacity to function as CSs and elicit (intravenous) cocaine conditioned approach and used this paradigm to test the role of NMDA receptor stimulation in the acquisition of cocaine conditioned approach. Rats were injected systemically with the NMDA receptor antagonist, MK-801, before the start of 4 consecutive conditioning sessions, each of which consisted of 20 randomly presented light/tone (CS) presentations paired with cocaine infusion contingent upon nose pokes...
November 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29154484/memantine-loaded-pegylated-biodegradable-nanoparticles-for-the-treatment-of-glaucoma
#2
Elena Sánchez-López, Maria Antonia Egea, Benjamin Michael Davis, Li Guo, Marta Espina, Amelia Maria Silva, Ana Cristina Calpena, Eliana Maria Barbosa Souto, Nivedita Ravindran, Miren Ettcheto, Antonio Camins, Maria Luisa García, Maria Francesca Cordeiro
Glaucoma is a multifactorial neurodegenerative disease associated with retinal ganglion cells (RGC) loss. Increasing reports of similarities in glaucoma and other neurodegenerative conditions have led to speculation that therapies for brain neurodegenerative disorders may also have potential as glaucoma therapies. Memantine is an N-methyl-d-aspartate (NMDA) antagonist approved for Alzheimer's disease treatment. Glutamate-induced excitotoxicity is implicated in glaucoma and NMDA receptor antagonism is advocated as a potential strategy for RGC preservation...
November 20, 2017: Small
https://www.readbyqxmd.com/read/29153599/lps-induced-cortical-kynurenic-acid-and-neurogranin-nfat-signaling-is-associated-with-deficits-in-stimulus-processing-during-pavlovian-conditioning
#3
A Oliveros, K Wininger, J Sens, M K Larsson, X C Liu, S Choi, A Faka, L Schwieler, G Engberg, S Erhardt, D S Choi
The N-Methyl-d-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT)...
December 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29146480/neuroprotection-by-chotosan-a-kampo-formula-against-glutamate-excitotoxicity-involves-the-inhibition-of-glun2b-but-not-glun2a-containing-nmda-receptor-mediated-responses-in-primary-cultured-cortical-neurons
#4
Sachie Sasaki-Hamada, Azusa Suzuki, Emi Sanai, Kinzo Matsumoto, Jun-Ichiro Oka
Chotosan (CTS), a traditional herbal formula called Kampo medicine, was shown to be effective in the treatment of vascular dementia in a clinical study, and exerted protective effects against transient cerebral ischemia-induced cognitive impairment in mice. In the present study, we investigated the neuroprotective effects of CTS using primary cultured rat cortical neurons. CTS (250-1000 μg/mL) inhibited neuronal death induced by 100 μM glutamate. This glutamate-induced neuronal death was blocked by a GluN2B-, but not GluN2A-containing NMDA receptor antagonist...
November 1, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29143219/glutamatergic-gabaergic-and-endocannabinoid-neurotransmissions-within-the-dorsal-hippocampus-modulate-the-cardiac-baroreflex-function-in-rats
#5
Nilson Carlos Ferreira-Junior, Davi Campos Lagatta, Leonardo Barbosa Moraes Resstel
The dorsal hippocampus (DH) is involved in the modulation of the cardiac baroreflex function. There is a wide expression of the NMDA and AMPA/Kainate receptors within the DH. Glutamate administration into the DH triggers both tachycardia and pressor responses. Moreover, GABAergic interneurons and endocannabinoid system play an important role in modulation of the activity of glutamatergic neurons within the DH. Therefore, the present work aimed to evaluate the involvement of the glutamatergic, GABAergic, and endocannabinoid neurotransmissions within the DH in cardiac baroreflex function in rats...
November 15, 2017: Pflügers Archiv: European Journal of Physiology
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
#6
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/29133852/nitrosynapsin-therapy-for-a-mouse-mef2c-haploinsufficiency-model-of-human-autism
#7
Shichun Tu, Mohd Waseem Akhtar, Rosa Maria Escorihuela, Alejandro Amador-Arjona, Vivek Swarup, James Parker, Jeffrey D Zaremba, Timothy Holland, Neha Bansal, Daniel R Holohan, Kevin Lopez, Scott D Ryan, Shing Fai Chan, Li Yan, Xiaofei Zhang, Xiayu Huang, Abdullah Sultan, Scott R McKercher, Rajesh Ambasudhan, Huaxi Xu, Yuqiang Wang, Daniel H Geschwind, Amanda J Roberts, Alexey V Terskikh, Robert A Rissman, Eliezer Masliah, Stuart A Lipton, Nobuki Nakanishi
Transcription factor MEF2C regulates multiple genes linked to autism spectrum disorder (ASD), and human MEF2C haploinsufficiency results in ASD, intellectual disability, and epilepsy. However, molecular mechanisms underlying MEF2C haploinsufficiency syndrome remain poorly understood. Here we report that Mef2c (+/-)(Mef2c-het) mice exhibit behavioral deficits resembling those of human patients. Gene expression analyses on brains from these mice show changes in genes associated with neurogenesis, synapse formation, and neuronal cell death...
November 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29129792/the-hypoxia-mimetic-protocatechuic-acid-ethyl-ester-inhibits-synaptic-signaling-and-plasticity-in-the-rat-hippocampus
#8
Sinead M Lanigan, John J O'Connor
During hypoxia a number of physiological changes occur within neurons including the stabilization of hypoxia-inducible factors (HIFs). The activity of these proteins is regulated by O2, Fe(2+), 2-OG and ascorbate-dependant hydroxylases which contain prolyl-4-hydroxylase domains (PHDs). PHD inhibitors have been widely used and have been shown to have a preconditioning and protective effect against a later and more severe hypoxic insult. In this study we have investigated the neuroprotective effects of the PHD inhibitor, protocatechuic acid ethyl ester (ethyl 3,4, dihydroxybenzoate: EDHB) as well as its effects on synaptic transmission and plasticity in the rat hippocampus using electrophysiological techniques...
November 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/29128144/the-antipsychotic-drug-brexpiprazole-reverses-phencyclidine-induced-disruptions-of-thalamocortical-networks
#9
Hanna E van den Munkhof, Jørn Arnt, Pau Celada, Francesc Artigas
Brexpiprazole (BREX), a recently approved antipsychotic drug in the US and Canada, improves cognitive dysfunction in animal models, by still largely unknown mechanisms. BREX is a partial agonist at 5-HT1A and D2 receptors and antagonist at α1B- and α2C-adrenergic and 5-HT2A receptors all with a similar potency. The NMDA receptor antagonist phencyclidine (PCP), used as pharmacological model of schizophrenia, activates thalamocortical networks and decreases low frequency oscillations (LFO; <4 Hz). These effects are reversed by antipsychotics...
November 8, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29127015/oxotremorine-m-potentiates-nmda-receptors-by-muscarinic-receptor-dependent-and-independent-mechanisms
#10
Ruud Zwart, Hannah Reed, Emanuele Sher
Muscarinic acetylcholine M1 receptors play an important role in synaptic plasticity in the hippocampus and cortex. Potentiation of NMDA receptors as a consequence of muscarinic acetylcholine M1 receptor activation is a crucial event mediating the cholinergic modulation of synaptic plasticity, which is a cellular mechanism for learning and memory. In Alzheimer's disease, the cholinergic input to the hippocampus and cortex is severely degenerated, and agonists or positive allosteric modulators of M1 receptors are therefore thought to be of potential use to treat the deficits in cognitive functions in Alzheimer's disease...
November 7, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29127002/post-acquisition-hippocampal-blockade-of-the-nmda-receptor-subunit-glun2a-but-not-glun2b-sustains-spatial-reference-memory-retention
#11
Keisuke Shinohara, Toshimichi Hata
While it has been shown that the blockade of N-methyl-d-aspartate type glutamate receptors (NMDARs) impairs memory acquisition, recent studies have reported that the post-acquisition administration of NMDAR antagonists suppresses spatial memory decay. These findings suggest that NMDARs are important not only for the acquisition of new memories but also for the decay of previously acquired memories. The present study investigated the contributions of specific NMDAR subunits to spatial memory decay using NVP-AAM077 (NVP), an NMDAR antagonist that preferentially binds to GluN2A subunits, and the selective GluN2B blocker Ro 25-6981 (Ro)...
November 7, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29126954/quantitative-analysis-of-kynurenine-aminotransferase-ii-in-the-adult-rat-brain-reveals-high-expression-in-proliferative-zones-and-corpus-callosum
#12
Chang Song, Sarah M Clark, Chloe N Vaughn, James D Nicholson, Kelley J Murphy, Ta-Chung M Mou, Robert Schwarcz, Gloria E Hoffman, Leonardo H Tonelli
Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan degradation, acts as an endogenous antagonist of alpha7 nicotinic and NMDA receptors and is implicated in a number of neurophysiological and neuropathological processes including cognition and neurodegenerative events. Therefore, kynurenine aminotransferase II (KAT II/AADAT), the enzyme responsible for the formation of the majority of neuroactive kynurenic acid in the brain, has prompted significant interest. Using immunohistochemistry, this enzyme was localized primarily in astrocytes throughout the adult rat brain, but detailed neuroanatomical studies are lacking...
November 8, 2017: Neuroscience
https://www.readbyqxmd.com/read/29124681/synergistic-toxicity-of-the-neurometabolites-quinolinic-acid-and-homocysteine-in-cortical-neurons-and-astrocytes-implications-in-alzheimer-s-disease
#13
Paula Pierozan, Helena Biasibetti-Brendler, Felipe Schmitz, Fernanda Ferreira, Carlos Alexandre Netto, Angela T S Wyse
The brain of patients affected by Alzheimer's disease (AD) develops progressive neurodegeneration linked to the formation of proteins aggregates. However, their single actions cannot explain the extent of brain damage observed in this disorder, and the characterization of co-adjuvant involved in the early toxic processes evoked in AD is essential. In this line, quinolinic acid (QUIN) and homocysteine (Hcy) appear to be involved in the AD neuropathogenesis. Herein, we investigate the effects of QUIN and Hcy on early toxic events in cortical neurons and astrocytes...
November 9, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29116600/recent-progress-in-the-pharmacotherapy-of-alzheimer-s-disease
#14
Rita Khoury, Kush Patel, Jake Gold, Stephanie Hinds, George T Grossberg
Alzheimer's disease is the most common major neurocognitive disorder with substantial social and economic impacts. This article is an update on current pharmacotherapy, advancements in biomarker use, and drugs in the pipeline for this disease. To date, no new drug has qualified to be added to the current therapeutic arsenal comprising cholinesterase inhibitors and the NMDA receptor antagonist memantine. Drugs in the pipeline include symptomatic therapies that are neurotransmitter-based, but mostly disease-modifying therapies...
November 7, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/29116427/cart-neurons-in-the-lateral-hypothalamus-communicate-with-the-nucleus-accumbens-shell-via-glutamatergic-neurons-in-paraventricular-thalamic-nucleus-to-modulate-reward-behavior
#15
Amit G Choudhary, Amita R Somalwar, Sneha Sagarkar, Abhishek Rale, Amul Sakharkar, Nishikant K Subhedar, Dadasaheb M Kokare
Paraventricular thalamic nucleus (PVT) serves as a transit node processing food and drug-associated reward information, but its afferents and efferents have not been fully defined. We test the hypothesis that the CART neurons in the lateral hypothalamus (LH) project to the PVT neurons, which in turn communicate via the glutamatergic fibers with the nucleus accumbens shell (AcbSh), the canonical site for reward. Rats conditioned to self-stimulate via an electrode in the right LH-medial forebrain bundle were used...
November 7, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29115658/combined-and-individual-use-of-pancaspase-inhibitor-q-vd-oph-and-nmda-receptor-antagonist-riluzole-in-experimental-spinal-cord-injury
#16
Halil Can, Aydın Aydoseli, Cengiz Gömleksiz, Burcu Göker, Muhittin Emre Altunrende, Müge Dolgun, Altay Sencer
BACKGROUND: We investigated the effects of an N-methyl-D-aspartate receptor antagonist, riluzole, and a pancaspase inhibitor and basic apoptosis mediator, Q-VD-OPh, in combination or alone in posttraumatic spinal cord injury. METHODS: In our study, 45 healthy male Sprague Dawley rats were used. Spinal trauma was induced by the clip compression technique via thoracal 7, 8, 9 laminectomies. After inducing the trauma, the drug was continuously administered intraperitoneally for 5 days...
2017: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/29112734/memantine-prevents-acute-radiation-induced-toxicities-at-hippocampal-excitatory-synapses
#17
Joseph G Duman, Jeffrey Dinh, Wei Zhou, Henry Cham, Vasilis C Mavratsas, Matea Paveškovic, Shalaka Mulherkar, Susan L McGovern, Kimberley F Tolias, David R Grosshans
Background: Memantine has shown clinical utility in preventing radiation-induced cognitive impairment, but the mechanisms underlying its protective effects remain unknown. We hypothesized that abnormal glutamate signaling causes radiation-induced abnormalities in neuronal structure and that memantine prevents synaptic toxicity. Methods: Hippocampal cultures expressing eGFP were irradiated or sham-treated and their dendritic spine morphology assessed at acute (minutes) and later (days) times using high-resolution confocal microscopy...
November 2, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/29112047/memantine-an-nmda-receptor-antagonist-prevents-thyroxin-induced-hypertension-but-not-cardiac-remodeling
#18
Steven J Repas, Nancy S Saad, Paul M L Janssen, Mohammad T Elnakish
Stimulation of glutamatergic tone has been causally linked to myocardial pathogenesis and amplified systemic blood pressure (BP). Memantine, a noncompetitive N-methyl-D-aspartate glutamatergic receptor (NMDA-R) antagonist, has been proposed to be an active cardioprotective drug. However, the efficacy of memantine and subsequently the possible involvement of the NMDA-R in the thyroxin (T4)-induced cardiovascular complications have never been investigated. We examined the effect of memantine (30 mg·kg·d) on the T4 (500 μg·kg·d)-provoked increase in mouse BP, cardiac hypertrophy indicated by enlarged overall myocardial mass, and reformed reactions of the contractile myocardium both in vivo and ex vivo after 2 weeks of treatment...
November 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29106383/s-sulfocysteine-nmda-receptor-dependentsignaling-underlies-neurodegeneration-in-molybdenum-cofactor-deficiency
#19
Avadh Kumar, Borislav Dejanovic, Florian Hetsch, Marcus Semtner, Debora Fusca, Sita Arjune, Jose Angel Santamaria-Araujo, Aline Winkelmann, Scott Ayton, Ashley I Bush, Peter Kloppenburg, Jochen C Meier, Guenter Schwarz, Abdel Ali Belaidi
Molybdenum cofactor deficiency (MoCD) is an autosomal recessive inborn error of metabolism characterized by neurodegeneration and death in early childhood. The rapid and progressive neurodegeneration in MoCD presents a major clinical challenge and may relate to the poor understanding of the molecular mechanisms involved. Recently, we reported that treating patients with cyclic pyranopterin monophosphate (cPMP) is a successful therapy for a subset of infants with MoCD and prevents irreversible brain damage. Here, we studied S-sulfocysteine (SSC), a structural analog of glutamate that accumulates in the plasma and urine of patients with MoCD, and demonstrated that it acts as an N-methyl D-aspartate receptor (NMDA-R) agonist, leading to calcium influx and downstream cell signaling events and neurotoxicity...
November 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29102713/the-anticonvulsant-activity-and-cerebral-protection-of-chronic-lithium-chloride-via-nmda-receptor-nitric-oxide-and-phospho-erk
#20
Razieh Mohammad Jafari, Mohammad Hossein Ghahremani, Nastaran Rahimi, Amir Shadboorestan, Amir Rashidian, Jamileh Esmaeili, Shahram Ejtemaei Mehr, Ahmad Reza Dehpour
The underlying mechanisms for the neuroprotective effects of lithium chloride in neurodegenerative diseases such as seizures remain unknown. In present study the downstream signaling pathway of phospho-ERK/NMDA receptors/nitric oxide has been studied. For this purpose, acute and chronic effect of lithium in seizure animal model and the interaction of NMDA receptor antagonist (MK-801) and neuronal nitric oxide synthase (nNOS) inhibitor (7-NI) with these neuroprotection has been studied. Acute lithium administration showed pro-convulsive properties in pentylenetetrazole (PTZ)-induced seizure model while chronic treatment increased the seizure threshold significantly...
November 2, 2017: Brain Research Bulletin
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