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https://www.readbyqxmd.com/read/29053799/erythropoietin-induces-homeostatic-plasticity-at-hippocampal-synapses
#1
Raquel B Dias, Tiago M Rodrigues, Diogo M Rombo, Filipa F Ribeiro, Joana Rodrigues, Jennifer McGarvey, Catarina Orcinha, Jeremy M Henley, Ana M Sebastião
The cytokine erythropoietin (EPO) is the master regulator of erythropoiesis. Intriguingly, many studies have shown that the cognitive performance of patients receiving EPO for its hematopoietic effects is enhanced, which prompted the growing interest in the use of EPO-based strategies to treat neuropsychiatric disorders. EPO plays key roles in brain development and maturation, but also modulates synaptic transmission. However, the mechanisms underlying the latter have remained elusive. Here, we show that acute (40-60 min) exposure to EPO presynaptically downregulates spontaneous and afferent-evoked excitatory transmission, without affecting basal firing of action potentials...
July 5, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29046483/deficiency-of-shank2-causes-mania-like-behavior-that-responds-to-mood-stabilizers
#2
Andrea L Pappas, Alexandra L Bey, Xiaoming Wang, Mark Rossi, Yong Ho Kim, Haidun Yan, Fiona Porkka, Lara J Duffney, Samantha M Phillips, Xinyu Cao, Jin-Dong Ding, Ramona M Rodriguiz, Henry H Yin, Richard J Weinberg, Ru-Rong Ji, William C Wetsel, Yong-Hui Jiang
Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24-/- mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29045570/optogenetic-activation-of-the-infralimbic-cortex-suppresses-the-return-of-appetitive-pavlovian-conditioned-responding-following-extinction
#3
Franz R Villaruel, Franca Lacroix, Christian Sanio, Daniel W Sparks, C Andrew Chapman, Nadia Chaudhri
The infralimbic medial prefrontal cortex (IL) is important for suppressing learned behavior after extinction, but whether this function extends to responses acquired through appetitive Pavlovian conditioning is unclear. We trained male, Long-Evans rats to associate a white-noise conditional stimulus (CS; 10 s; 14 presentations per session) with 10% liquid sucrose (0.2 mL per CS presentation), and recorded entries into the fluid port during the CS. The CS was presented without sucrose in subsequent extinction and test sessions...
October 17, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/29042315/-interleukin-1-beta-reduces-glua1-phosphorylation-and-its-surface-expression-during-memory-reconsolidation-and-alpha-melanocyte-stimulating-hormone-can-modulate-these-effects
#4
Ivana Machado, Helgi B Schiöth, Mercedes Lasaga, Teresa Scimonelli
Pro-inflammatory cytokines can affect cognitive processes such as learning and memory. Particularly, interleukin-1β (IL-1β) influences hippocampus-dependent memories. We previously reported that administration of IL-1β in dorsal hippocampus impaired contextual fear memory reconsolidation. This effect was reversed by the melanocortin alpha-melanocyte-stimulating hormone (α-MSH). Our results also demonstrated that IL-1β produced a significant decrease in glutamate release from dorsal hippocampus synaptosomes after reactivation of the fear memory...
October 14, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29042088/distribution-of-glyphosate-and-aminomethylphosphonic-acid-ampa-in-agricultural-topsoils-of-the-european-union
#5
Vera Silva, Luca Montanarella, Arwyn Jones, Oihane Fernández-Ugalde, Hans G J Mol, Coen J Ritsema, Violette Geissen
Approval for glyphosate-based herbicides in the European Union (EU) is under intense debate due to concern about their effects on the environment and human health. The occurrence of glyphosate residues in European water bodies is rather well documented whereas only few, fragmented and outdated information is available for European soils. We provide the first large-scale assessment of distribution (occurrence and concentrations) of glyphosate and its main metabolite aminomethylphosphonic acid (AMPA) in EU agricultural topsoils, and estimate their potential spreading by wind and water erosion...
October 14, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/29033800/stimulation-of-cortico-subthalamic-projections-amplifies-resting-motor-circuit-activity-and-leads-to-increased-locomotion-in-dopamine-depleted-mice
#6
Teresa H Sanders
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in patients with Parkinson's disease (PD). STN-DBS enables similar improved motor function, including increased movement speed (reduced bradykinesia), in the 6-OHDA dopamine-depletion mouse model of PD. Previous analyses of electrophysiological recordings from STN and motor cortex (M1) have explored signaling changes that correspond to PD and amelioration of PD symptoms. The most common results show an increase in beta frequency power during 'off' states and a reduction in beta during 'on' states...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29033788/zinc-as-a-neuromodulator-in-the-central-nervous-system-with-a-focus-on-the-olfactory-bulb
#7
REVIEW
Laura J Blakemore, Paul Q Trombley
The olfactory bulb (OB) is central to the sense of smell, as it is the site of the first synaptic relay involved in the processing of odor information. Odor sensations are first transduced by olfactory sensory neurons (OSNs) before being transmitted, by way of the OB, to higher olfactory centers that mediate olfactory discrimination and perception. Zinc is a common trace element, and it is highly concentrated in the synaptic vesicles of subsets of glutamatergic neurons in some brain regions including the hippocampus and OB...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29032200/sez6l2-regulates-phosphorylation-of-add-and-neuritogenesis
#8
Hiroaki Yaguchi, Ichiro Yabe, Hidehisa Takahashi, Masashi Watanabe, Taichi Nomura, Takahiro Kano, Masaki Matsumoto, Keiichi I Nakayama, Masahiko Watanabe, Shigetsugu Hatakeyama
Increasing evidence shows that immune-mediated mechanisms may contribute to the pathogenesis of central nervous system disorders including cerebella ataxias, as indicated by the aberrant production of neuronal surface antibodies. We previously reported a patient with cerebellar ataxia associated with production of a new anti-neuronal antibody, anti-seizure-related 6 homolog like 2 (Sez6l2). Sez6l2 is a type 1 membrane protein that is highly expressed in the hippocampus and cerebellar cortex and mice lacking Sez6l2 protein family members develop ataxia...
October 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29031852/inhibition-of-cdk5-rejuvenates-inhibitory-circuits-and-restores-experience-dependent-plasticity-in-adult-visual-cortex
#9
Yue Li, Laijian Wang, Xinxin Zhang, Mengyao Huang, Sitong Li, Xinxing Wang, Lin Chen, Bin Jiang, Yupeng Yang
Cyclin-dependent kinase 5 (Cdk5) acts as an essential modulator for neural development and neurological disorders. Here we show that Cdk5 plays a pivotal role in modulating GABAergic signaling and the maturation of visual system. In adult mouse primary visual cortex, Cdk5 formed complex with the GABA synthetic enzyme glutamate decarboxylase GAD67, but not with GAD65. In addition to enhancement in the surface level of NR2B-containing NMDA receptors, inhibition of Cdk5 reduced the protein levels of GADs and Otx2, while leaving intact the expression of vesicular GABA transporter and subunits of GABAA or AMPA receptors...
October 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29030286/peptides-acting-as-cognitive-enhancers
#10
Diego Asua, Ghassen Bougamra, María Calleja, Miguel Morales, Shira Knafo
The aim of this paper is to present an overview of three peptides that, by improving synaptic function, enhance learning and memory in laboratory rodents. We summarize their structure, their mechanisms of action, and their effects on synaptic and cognitive function. First we describe FGL, a peptide derived from the neural cell adhesion molecule which improves cognition by the activation of the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to the synapses. Then we describe PTD4-PI3KAc peptide that by activating PI3K signaling pathway it promotes synapse and spine formation and enhances hippocampal dependent memory...
October 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/29029261/selective-enhancement-of-domoic-acid-toxicity-in-primary-cultures-of-cerebellar-granule-cells-by-lowering-extracellular-na-concentration
#11
Anabel Pérez-Gómez, David Cabrera-García, Davide Warm, Ann M Marini, Javier Salas Puig, Maria Teresa Fernández-Sánchez, Antonello Novelli
Domoic acid (DOM) is an excitatory amino acid analog of kainic acid (KA) that acts through glutamic acid (GLU) receptors, inducing a fast and potent neurotoxic response. Here we present evidence for an enhancement of excitotoxicity following exposure of cultured cerebellar granule cells to DOM in the presence of lower than physiological Na+ concentrations. The concentration of DOM that reduced by 50% neuronal survival was ̴ 3 µM in Na+-free conditions and 16 µM in presence of a physiological concentration of extracellular Na+...
September 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29028184/native-kcc2-interactome-reveals-pacsin1-as-a-critical-regulator-of-synaptic-inhibition
#12
Vivek Mahadevan, C Sahara Khademullah, Zahra Dargaei, Jonah Chevrier, Pavel Uvarov, Julian Kwan, Richard D Bagshaw, Tony Pawson, Andrew Emili, Yves De Koninck, Victor Anggono, Matti Airaksinen, Melanie A Woodin
KCC2 is a neuron-specific K(+)-Cl(-) cotransporter essential for establishing the Cl(-) gradient required for hyperpolarizing inhibition in the central nervous system (CNS). KCC2 is highly localized to excitatory synapses where it regulates spine morphogenesis and AMPA receptor confinement. Aberrant KCC2 function contributes to human neurological disorders including epilepsy and neuropathic pain. Using functional proteomics, we identified the KCC2-interactome in the mouse brain to determine KCC2-protein interactions that regulate KCC2 function...
October 13, 2017: ELife
https://www.readbyqxmd.com/read/29024665/astrocyte-secreted-glypican-4-regulates-release-of-neuronal-pentraxin-1-from-axons-to-induce-functional-synapse-formation
#13
Isabella Farhy-Tselnicker, Adriana C M van Casteren, Aletheia Lee, Veronica T Chang, A Radu Aricescu, Nicola J Allen
The generation of precise synaptic connections between developing neurons is critical to the formation of functional neural circuits. Astrocyte-secreted glypican 4 induces formation of active excitatory synapses by recruiting AMPA glutamate receptors to the postsynaptic cell surface. We now identify the molecular mechanism of how glypican 4 exerts its effect. Glypican 4 induces release of the AMPA receptor clustering factor neuronal pentraxin 1 from presynaptic terminals by signaling through presynaptic protein tyrosine phosphatase receptor δ...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/29023170/ampa-receptors-and-perampanel-behind-selected-epilepsies-current-evidence-and-future-perspectives
#14
Carlo Di Bonaventura, Angelo Labate, Marta Maschio, Stefano Meletti, Emilio Russo
The alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors are the major mediators of glutamate-mediated excitatory neurotransmission, and are critical for synchronization and spread of epileptic activity. Areas covered: AMPA receptor antagonists have been also developed as antiepileptic drugs and perampanel (PER) is the first highly selective, non-competitive AMPA-type glutamate receptor antagonist that is available on the market. It is approved as adjunctive therapy for the treatment of partial-onset seizures with or without secondary generalization, and for primary generalized tonic-clonic seizures in idiopathic generalized epilepsy, in patients aged ≥ 12 years...
October 17, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29019035/concanavalin-a-induces-cortical-neuron-apoptosis-by-causing-ros-accumulation-and-tyrosine-kinase-activation
#15
Soyong Jang, Taddesse Yayeh, Yea-Hyun Leem, Eun-Mi Park, Yoshihisa Ito, Seikwan Oh
The lectin, concanavalin A (Con A), is the most extensively investigated member of the lectin family of plant proteins, but its effects on cortical neurons and astrocytes are poorly understood. In cultured cortical neurons and astrocytes, Con A exhibited dose-dependent neurotoxicity, but this was not observed in astrocytes. Similarly, in the cortical areas of rat brains, intracranial administration of Con A caused neuronal but no astrocyte damage. Methyl-α-D-mannopyranoside, a competitor of Con A, blocked Con A-induced cell death, whereas AMPA/KA receptor antagonists showed partial blocking effects...
October 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29019029/hippocampal-acetylation-may-improve-prenatal-stress-induced-depression-like-behavior-of-male-offspring-rats-through-regulating-ampars-expression
#16
Yong Lu, Junli Zhang, Lin Zhang, Shaokang Dang, Qian Su, Huiping Zhang, Tianwei Lin, Xiaoxiao Zhang, Yurong Zhang, Hongli Sun, Zhongliang Zhu, Hui Li
This study is to determine the role and mechanism of hippocampal acetylation in prenatal stress (PS) induced depression-like behavior of male offspring rats. PS-induced depression rat model was established. Sucrose preference and forced swim test were used to observe the behavior changes of male offspring rats. Hippocampal acetylation was induced by Trichostatin A injection. Quantitative real-time PCR and Western blot were used to determine the changes of AMPARs in acetylated hippocampus. The behavioral tests proved that AMPA was involved in the PS-induced depression-like behavior in offspring rats...
October 10, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/29016847/a-point-mutation-in-the-ion-conduction-pore-of-ampa-receptor-gria3-causes-dramatically-perturbed-sleep-patterns-as-well-as-intellectual-disability
#17
Benjamin Davies, Laurence A Brown, Ondrej Cais, Jake Watson, Amber J Clayton, Veronica T Chang, Daniel Biggs, Christopher Preece, Polinka Hernandez-Pliego, Jon Krohn, Amarjit Bhomra, Stephen R F Twigg, Andrew Rimmer, Alexander Kanapin, Arjune Sen, Zenobia Zaiwalla, Gil McVean, Russell Foster, Peter Donnelly, Jenny C Taylor, Edward Blair, David Nutt, A Radu Aricescu, Ingo H Greger, Stuart N Peirson, Jonathan Flint, Hilary C Martin
The discovery of genetic variants influencing sleep patterns can shed light on the physiological processes underlying sleep. As part of a large clinical sequencing project, WGS500, we sequenced a family in which the two male children had severe developmental delay and a dramatically disturbed sleep-wake cycle, with very long wake and sleep durations, reaching up to 106-h awake and 48-h asleep. The most likely causal variant identified was a novel missense variant in the X-linked GRIA3 gene, which has been implicated in intellectual disability...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28993263/angiotensin-1-7-in-the-rostro-ventrolateral-medulla-increases-blood-pressure-and-splanchnic-sympathetic-nerve-activity-in-anesthetized-rats
#18
Mark S Bilodeau, J C Leiter
Angiotensin 1-7 (ANG-(1-7)), a derivative of angiotensin I or II, is involved in the propagation of sympathetic output to the heart and vasculature, and the receptor for ANG-(1-7), the Mas receptor, is expressed on astrocytes in the rostral ventrolateral medulla (RVLM). We recorded blood pressure (BP) and splanchnic sympathetic nerve activity (SSNA) before and after focal injection of ANG-(1-7) into the RVLM of rats. Unilateral injection of ANG-(1-7) into the RVLM, acting through the Mas receptor, increased SSNA and BP, and glutamate receptor antagonists, CNQX and D-AP5, partially reduced the ANG-(1-7) effect...
October 6, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28989605/n-n-dimethylation-of-nitrobenzenes-with-co2-and-water-by-electrocatalysis
#19
Xiaofu Sun, Qinggong Zhu, Jiayin Hu, Xinchen Kang, Jun Ma, Huizhen Liu, Buxing Han
We have proposed a strategy for the synthesis of N,N-dimethylanilines from nitrobenzene and its derivatives, CO2, and water via an electrochemical reaction under ambient conditions. H(+) generated from H2O was used as the hydrogen source. Pd/Co-N/carbon, in which the Pd nanoparticles were supported on Co-N/carbon, was designed and used as the electrocatalyst. It was found that the electrocatalyst was very efficient for the reaction in MeCN solution with 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Bmim]Tf2N) as the supporting electrolyte and 1-amino-methylphosphonic acid (AMPA) as the thermal co-catalyst...
August 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28987594/auxiliary-subunits-of-ampa-receptors-the-discovery-of-a-forebrain-selective-antagonist-ly3130481-cerc-611
#20
REVIEW
Akihiko S Kato, Jeffrey M Witkin
Drugs originate from the discovery of compounds, natural or synthetic, that bind to proteins (receptors, enzymes, transporters, etc.) The interaction of which modulates biological cascades that have potential therapeutic benefit. Rational strategies in identifying novel drug therapies are typically based on knowledge of the structure of the target proteins and the design of new chemical entities that modulate these proteins in a beneficial manner. The present review discusses a novel approach to drug discovery based on the identification and characterization of auxiliary proteins, the transmembrane AMPA receptor regulatory proteins (TARPs) that are associated with AMPA receptors, which led to the discovery of the TARP-dependent-AMPA forebrain selective receptor antagonist (TDAA), LY3130481/CERC-611 that is currently in clinical development for epilepsy...
October 4, 2017: Biochemical Pharmacology
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