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https://www.readbyqxmd.com/read/28633291/p2x7-receptors-drive-spine-synapse-plasticity-in-the-learned-helplessness-model-of-depression
#1
L Otrokocsi, Á Kittel, B Sperlágh
Background: Major depressive disorder is characterized by structural and functional abnormalities of cortical and limbic brain areas, including a decrease in spine synapse number in the dentate gyrus (DG) of the hippocampus. Recent studies highlighted that both genetic and pharmacological invalidation of the purinergic P2X7 receptor (P2rx7) leads to antidepressant-like phenotype in animal experiments, however, the impact of P2rx7 on depression-related structural changes in the hippocampus is not clarified yet...
June 13, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28614711/dapk1-mediates-ltd-by-making-camkii-glun2b-binding-ltp-specific
#2
Dayton J Goodell, Vincent Zaegel, Steven J Coultrap, Johannes W Hell, K Ulrich Bayer
The death-associated protein kinase 1 (DAPK1) is a potent mediator of neuronal cell death. Here, we find that DAPK1 also functions in synaptic plasticity by regulating the Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII and T286 autophosphorylation are required for both long-term potentiation (LTP) and depression (LTD), two opposing forms of synaptic plasticity underlying learning, memory, and cognition. T286-autophosphorylation induces CaMKII binding to the NMDA receptor (NMDAR) subunit GluN2B, which mediates CaMKII synaptic accumulation during LTP...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28602919/the-fine-tuning-of-retinocollicular-topography-depends-on-reelin-signaling-during-early-postnatal-development-of-the-rat-visual-system
#3
Rachel Antonioli-Santos, Bruna Lanzillotta-Mattos, Cecília Hedin-Pereira, Claudio Alberto Serfaty
During postnatal development, neural circuits are extremely dynamic and develop precise connection patterns that emerge as a result of the elimination of synaptic terminals, a process instructed by molecular cues and patterns of electrical activity. In the rodent visual system, this process begins during the first postnatal week and proceeds during the second and third postnatal weeks as spontaneous retinal activity and finally use dependent fine tuning takes place. Reelin is a large extracellular matrix glycoprotein able to affect several steps of brain development, from neuronal migration to the maturation of dendritic spines and use-dependent synaptic development...
June 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/28598327/co-agonists-differentially-tune-glun2b-nmda-receptor-trafficking-at-hippocampal-synapses
#4
Joana S Ferreira, Thomas Papouin, Laurent Ladépêche, Andrea Yao, Valentin C Langlais, Delphine Bouchet, Jérôme Dulong, Jean-Pierre Mothet, Silvia Sacchi, Loredano Pollegioni, Pierre Paoletti, Stéphane Henri Richard Oliet, Laurent Groc
The subunit composition of synaptic NMDA receptors (NMDAR), such as the relative content of GluN2A- and GluN2B-containing receptors, greatly influences the glutamate synaptic transmission. Receptor co-agonists, glycine and D-serine, have intriguingly emerged as potential regulators of the receptor trafficking in addition to their requirement for its activation. Using a combination of single-molecule imaging, biochemistry and electrophysiology, we show that glycine and D-serine relative availability at rat hippocampal glutamatergic synapses regulate the trafficking and synaptic content of NMDAR subtypes...
June 9, 2017: ELife
https://www.readbyqxmd.com/read/28594961/pirb-regulates-asymmetries-in-hippocampal-circuitry
#5
Hikari Ukai, Aiko Kawahara, Keiko Hirayama, Matthew Julian Case, Shotaro Aino, Masahiro Miyabe, Ken Wakita, Ryohei Oogi, Michiyo Kasayuki, Shihomi Kawashima, Shunichi Sugimoto, Kanako Chikamatsu, Noritaka Nitta, Tsuneyuki Koga, Ryuichi Shigemoto, Toshiyuki Takai, Isao Ito
Left-right asymmetry is a fundamental feature of higher-order brain structure; however, the molecular basis of brain asymmetry remains unclear. We recently identified structural and functional asymmetries in mouse hippocampal circuitry that result from the asymmetrical distribution of two distinct populations of pyramidal cell synapses that differ in the density of the NMDA receptor subunit GluRε2 (also known as NR2B, GRIN2B or GluN2B). By examining the synaptic distribution of ε2 subunits, we previously found that β2-microglobulin-deficient mice, which lack cell surface expression of the vast majority of major histocompatibility complex class I (MHCI) proteins, do not exhibit circuit asymmetry...
2017: PloS One
https://www.readbyqxmd.com/read/28594440/calcium-signalling-in-medial-intercalated-cell-dendrites-and-spines
#6
Cornelia Strobel, Robert K P Sullivan, Peter Stratton, Pankaj Sah
The amygdala plays a central role in fear conditioning and extinction. The medial intercalated (mITC) neurons are GABAergic cell clusters interspaced between the basolateral (BLA) and central amygdala (CeA). These neurons are thought to play a key role in fear and extinction, controlling the output of the CeA by feed-forward inhibition. BLA to mITC cell inputs are though to undergo synaptic plasticity, a mechanism underlying learning, which is mediated by NMDA-receptor dependent mechanisms that require changes in cytosolic calcium...
June 8, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28588488/antinociceptive-activity-of-borreria-verticillata-in-vivo-and-in-silico-studies
#7
Rosa H M Silva, Nathália de Fátima M Lima, Alberto J O Lopes, Cleydlenne C Vasconcelos, José W C de Mesquita, Ludmilla S S de Mesquita, Fernando C V M Lima, Maria N de S Ribeiro, Ricardo M Ramos, Maria do Socorro de S Cartágenes, João B S Garcia
Borreria verticillata (L.) G. Mey. known vassourinha has antibacterial, antimalarial, hepatoprotective, antioxidative, analgesic, and anti-inflammatory, however, its antinociceptive action requires further studies. Aim of the study evaluated the antinociceptive activity of B. verticillata hydroalcoholic extract (EHBv) and ethyl acetate fraction (FAc) by in vivo and in silico studies. In vivo assessment included the paw edema test, writhing test, formalin test and tail flick test. Wistar rats and Swiss mice were divided into 6 groups and given the following treatments oral: 0...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28588066/identification-of-aicp-as-a-glun2c-selective-nmda-receptor-superagonist-at-the-glun1-glycine-site
#8
Maja Jessen, Kristen Frederiksen, Feng Yi, Rasmus P Clausen, Kasper B Hansen, Hans Brauner-Osborne, Paul Kilburn, Anders Damholt
NMDA-type ionotropic glutamate receptors mediate excitatory neurotransmission in the central nervous system and are critically involved in brain function. NMDA receptors are also implicated in psychiatric and neurological disorders and have received considerable attention as therapeutic targets. In this regard, administration of D-cycloserine (DCS), which is a glycine site NMDA receptor agonist, can enhance extinction of conditioned fear responses. The intriguing behavioral effects of DCS have been linked to its unique pharmacological profile among NMDA receptor subtypes (GluN1/2A-D), in which DCS is a superagonist at GluN2C-containing receptors compared to glycine and a partial agonist at GluN2B-containing receptors...
June 6, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28586221/the-structure-activity-relationship-of-a-tetrahydroisoquinoline-class-of-n-methyl-%C3%A1-aspartate-receptor-modulators-that-potentiates-glun2b-containing-n-methyl-%C3%A1-aspartate-receptors
#9
Katie L Strong, Matthew P Epplin, John Bacsa, Christopher J Butch, Pieter B Burger, David S Menaldino, Stephen F Traynelis, Dennis C Liotta
We have identified a series of positive allosteric NMDA receptor (NMDAR) modulators derived from a known class of GluN2C/D-selective tetrahydroisoquinoline analogues that includes CIQ. The prototypical compound of this series contains a single isopropoxy moiety in place of the two methoxy substituents present in CIQ. Modifications of this isopropoxy-containing scaffold led to the identification of analogues with enhanced activity at the GluN2B subunit. We identified molecules that potentiate the response of GluN2B/GluN2C/GluN2D, GluN2B/GluN2C, and GluN2C/GluN2D-containing NMDARs to maximally effective concentrations of agonist...
June 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28585567/role-of-src-family-kinases-in-bdnf-mediated-suppression-of-cocaine-seeking-and-prevention-of-cocaine-induced-erk-glun2a-and-glun2b-dephosphorylation-in-the-prelimbic-cortex
#10
Sarah M Barry, Jacqueline F McGinty
Models of relapse have demonstrated that neuroadaptations in reward circuits following cocaine self-administration underlie reinstatement of drug seeking. Dysregulation of the pathway from the prelimbic cortex to the nucleus accumbens is implicated in reinstatement. A single BDNF infusion into the prelimbic cortex following a final cocaine self-administration session results in attenuation of reinstatement of cocaine-seeking. Inhibiting BDNF's receptor, TrkB, ERK/MAP kinase activation, or NMDA receptors blocks this attenuating effect, indicating that the interaction between glutamate-mediated synaptic activity and TrkB signaling is imperative to BDNF's suppressive effect on drug-seeking...
June 6, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28582391/all-atom-nmda-receptor-transmembrane-domain-model-development-and-simulations-in-lipid-bilayers-and-water
#11
Samaneh Mesbahi-Vasey, Lea Veras, Michael Yonkunas, Jon W Johnson, Maria G Kurnikova
N-methyl-d-aspartate receptors (NMDARs) are members of the ionotropic glutamate receptor family that mediate excitatory synaptic transmission in the central nervous system. The channels of NMDARs are permeable to Ca2+ but blocked by Mg2+, distinctive properties that underlie essential brain processes such as induction of synaptic plasticity. However, due to limited structural information about the NMDAR transmembrane ion channel forming domain, the mechanism of divalent cation permeation and block is understood poorly...
2017: PloS One
https://www.readbyqxmd.com/read/28554889/development-of-glutamatergic-proteins-in-human-visual-cortex-across-the-lifespan
#12
Caitlin R Siu, Simon P Beshara, David G Jones, Kathryn M Murphy
Traditionally, human primary visual cortex (V1) has been thought to mature within the first few years of life, based on anatomical studies of synapse formation, and establishment of intra- and inter-cortical connections. Human vision, however, develops well beyond the first few years. Previously, we found prolonged development of some GABAergic proteins in human V1 (Pinto et al., 2010). Yet as over 80% of synapses in V1 are excitatory, it remains unanswered if the majority of synapses regulating experience-dependent plasticity and receptive field properties develop late like their inhibitory counterparts...
May 29, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28535798/using-kalirin-conditional-knockout-mice-to-distinguish-its-role-in-dopamine-receptor-mediated-behaviors
#13
Taylor P LaRese, Yan Yan, Betty A Eipper, Richard E Mains
BACKGROUND: Mice lacking Kalirin-7 (Kal7(KO)), a Rho GDP/GTP exchange factor, self-administer cocaine at a higher rate than wildtype mice, and show an exaggerated locomotor response to experimenter-administered cocaine. Kal7, which localizes to post-synaptic densities at glutamatergic synapses, interacts directly with the GluN2B subunit of the N-methyl-D-aspartate (NMDA; GluN) receptor. Consistent with these observations, Kal7 plays an essential role in NMDA receptor dependent long term potentiation and depression, and glutamatergic transmission plays a key role in the response to chronic cocaine...
May 23, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28533163/grin2b-gain-of-function-mutations-are-sensitive-to-radiprodil-a-negative-allosteric-modulator-of-glun2b-containing-nmda-receptors
#14
Brice Mullier, Christian Wolff, Zara Amanda Sands, Philippe Ghisdal, Pierandrea Muglia, Rafal Marian Kaminski, Véronique Marie André
De novo gain of function mutations in GRIN2B encoding the GluN2B subunit of the N-methyl-d-aspartate (NMDA) receptor have been linked with epileptic encephalopathies, including infantile spasms. We investigated the effects of radiprodil, a selective GluN2B negative allosteric modulator and other non-selective NMDA receptor inhibitors on glutamate currents mediated by NMDA receptors containing mutated GluN2B subunits. The experiments were performed in Xenopus oocytes co-injected with the following human mRNAs: GRIN1/GRIN2B, GRIN1/GRIN2B-R540H, GRIN1/GRIN2B-N615I and GRIN1/GRIN2B-V618G...
May 19, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28526611/alcohol-induces-input-specific-aberrant-synaptic-plasticity-in-the-rat-dorsomedial-striatum
#15
Tengfei Ma, Britton Barbee, Xuehua Wang, Jun Wang
Accumulated evidence suggests that the dorsomedial striatum (DMS) of the basal ganglia plays an essential role in pathological excessive alcohol consumption. The DMS receives multiple glutamatergic inputs. However, whether and how alcohol consumption distinctly affects these excitatory afferents to the DMS remains unknown. Here, we used optogenetics to selectively activate the rat medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) inputs in DMS slices, and measured the effects of alcohol consumption on glutamatergic transmission in these corticostriatal and amygdalostriatal circuits...
May 17, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28526038/phosphorylation-of-tau-at-y18-but-not-tau-fyn-binding-is-required-for-tau-to-modulate-nmda-receptor-dependent-excitotoxicity-in-primary-neuronal-culture
#16
Takashi Miyamoto, Liana Stein, Reuben Thomas, Biljana Djukic, Praveen Taneja, Joseph Knox, Keith Vossel, Lennart Mucke
BACKGROUND: Hyperexcitability of neuronal networks can lead to excessive release of the excitatory neurotransmitter glutamate, which in turn can cause neuronal damage by overactivating NMDA-type glutamate receptors and related signaling pathways. This process (excitotoxicity) has been implicated in the pathogenesis of many neurological conditions, ranging from childhood epilepsies to stroke and neurodegenerative disorders such as Alzheimer's disease (AD). Reducing neuronal levels of the microtubule-associated protein tau counteracts network hyperexcitability of diverse causes, but whether this strategy can also diminish downstream excitotoxicity is less clear...
May 19, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28525360/role-of-sigma-1-receptor-in-high-fat-diet-induced-peripheral-neuropathy
#17
Tieying Song, Jianhui Zhao, Xiaojing Ma, Zaiwang Zhang, Bo Jiang, Yunliang Yang
The neurobiological mechanisms of obesity-induced peripheral neuropathy are poorly understood. We evaluated the role of Sigma-1 receptor (Sig-1R) and NMDA receptor (NMDARs) in the spinal cord in peripheral neuropathy using an animal model of high fat diet-induced diabetes. We examined the expression of Sig-1R and NMDAR subunits GluN2A and GluN2B along with postsynaptic density protein 95 (PSD-95) in the spinal cord after 24-week HFD treatment in both wild-type and Sig-1R-/- mice. Finally, we examined the effects of repeated intrathecal administrations of selective Sig-1R antagonists BD1047 in HFD-fed wild-type mice on peripheral neuropathy...
June 14, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28512860/intrinsic-cellular-and-molecular-properties-of-in-vivo-hippocampal-synaptic-plasticity-are-altered-in-the-absence-of-key-synaptic-matrix-molecules
#18
Stephan Jansen, Christine Gottschling, Andreas Faissner, Denise Manahan-Vaughan
Hippocampal synaptic plasticity comprises a key cellular mechanism for information storage. In the hippocampus, both long-term potentiation (LTP) and long-term depression (LTD) are triggered by synaptic Ca(2+) -elevations that are typically mediated by the opening of voltage-gated cation channels, such as N-methyl-D-aspartate receptors (NMDAR), in the postsynaptic density. The integrity of the post-synaptic density is ensured by the extracellular matrix (ECM). Here, we explored whether synaptic plasticity is affected in adult behaving mice that lack the ECM proteins brevican, neurocan, tenascin-C and tenascin-R (TG)...
May 17, 2017: Hippocampus
https://www.readbyqxmd.com/read/28511693/antagonistic-action-on-nmda-glun2b-mediated-currents-of-two-peptides-that-were-conantokin-g-structure-based-designed
#19
Edwin A Reyes-Guzman, Nohora Vega-Castro, Edgar A Reyes-Montaño, Esperanza Recio-Pinto
BACKGROUND: The GluN2B subunit of the N-methyl-D-aspartate receptor (NMDAr) modulates many physiological processes including learning, memory, and pain. Excessive increase in NMDAr/GluN2B activity has been associated with various disorders such neuropathic pain and neuronal death following hypoxia. Thus there is an interest in identifying NMDAr antagonists that interact specifically with the GluN2B subunit. Recently based on structural analysis between the GluN2B subunit and conantokin-G, a toxin that interacts selectively with the GluN2B subunit, we designed various peptides that are predicted to act as NMDAr antagonists by interacting with the GluN2B subunit...
May 16, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28511005/characterization-of-l-theanine-excitatory-actions-on-hippocampal-neurons-toward-the-generation-of-novel-n-methyl-d-aspartate-receptor-modulators-based-on-its-backbone
#20
Fatiha Sebih, Matthieu Rousset, Salima Bellahouel, Marc Rolland, Marie Celeste de Jesus Ferreira, Janique Guiramand, Catherine Cohen-Solal, Gérard Barbanel, Thierry Cens, Mohammed Abouazza, Adrien Tassou, Maud Gratuze, Céline Meusnier, Pierre Charnet, Michel Vignes, Valérie Rolland
l-Theanine (or l-γ-N-ethyl-glutamine) is the major amino acid found in Camellia sinensis. It has received much attention because of its pleiotropic physiological and pharmacological activities leading to health benefits in humans, especially. We describe here a new, easy, efficient, and environmentally friendly chemical synthesis of l-theanine and l-γ-N-propyl-Gln and their corresponding d-isomers. l-Theanine, and its derivatives obtained so far, exhibited partial coagonistic action at N-methyl-d-aspartate (NMDA) receptors, with no detectable agonist effect at other glutamate receptors, on cultured hippocampal neurons...
May 30, 2017: ACS Chemical Neuroscience
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