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https://www.readbyqxmd.com/read/29224956/bidirectional-shift-of-group-iii-metabotropic-glutamate-receptor-mediated-synaptic-depression-in-the-epileptic-hippocampus
#1
Fabian Dammann, Timo Kirschstein, Xiati Guli, Steffen Müller, Katrin Porath, Marco Rohde, Tursonjan Tokay, Rüdiger Köhling
A common function of group III metabotropic glutamate receptors (mGluRs) located at the presynaptic site of a glutamatergic synapse is synaptic depression. Here, we studied synaptic depression mediated by group III mGluR activation at Schaffer collateral-CA1 (SC-CA1) synapses and associational-commissural-CA3 (AC-CA3) synapses by recording field excitatory postsynaptic potentials in the in vitro brain slice preparation. In order to gauge the impact of synaptic depression in chronically epileptic tissue, we compared rats after pilocarpine-induced status epilepticus (post-SE) with control animals...
December 7, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/29221855/toll-like-receptor-4-regulates-anxiety-like-behavior-and-darpp-32-phosphorylation
#2
T Femenia, Y Qian, T Arentsen, H Forssberg, R Diaz Heijtz
Toll-like receptors (TLRs) play a crucial role in early innate immune responses to inflammatory agents and pathogens. In the brain, some members of the TLR family are expressed in glial cells and neurons. In particular, TLR4 has been involved in learning and memory processes, stress-induced adaptations, and pathogenesis of neurodegenerative disorders. However, the role of TLR4 in emotional behaviors and their underlying mechanisms are poorly understood. In this study, we investigated the role of TLR4 in emotional and social behavior by using different behavioral approaches, and assessed potential molecular alterations in important brain areas involved in emotional responses...
December 5, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29220747/effects-of-group-ii-metabotropic-glutamate-receptor-modulation-on-ethanol-and-sucrose-seeking-and-consumption-in-the-rat
#3
Kyle A Windisch, Cristine L Czachowski
Previous studies suggest that group II metabotropic glutamate receptors (mGluR2/3) are involved in regulating ethanol-seeking and consumption. The mGluR2/3 agonist LY379268 (LY37) and selective mGluR2 positive allosteric modulator biphenyl‑indanone A (BINA) were used to investigate the relative contribution of mGlu2 and mGlu3 receptors on ethanol- and sucrose-seeking and consumption. A microinjection study was then performed to examine the role of nucleus accumbens (NAc) core mGluR2/3 on ethanol-seeking. For the systemic experiments, separate groups of male Wistar rats [LY37 (0-2...
September 23, 2017: Alcohol
https://www.readbyqxmd.com/read/29213077/allosteric-nanobodies-uncover-a-role-of-hippocampal-mglu2-receptor-homodimers-in-contextual-fear-consolidation
#4
Pauline Scholler, Damien Nevoltris, Dimitri de Bundel, Simon Bossi, David Moreno-Delgado, Xavier Rovira, Thor C Møller, Driss El Moustaine, Michaël Mathieu, Emilie Blanc, Heather McLean, Elodie Dupuis, Gérard Mathis, Eric Trinquet, Hervé Daniel, Emmanuel Valjent, Daniel Baty, Patrick Chames, Philippe Rondard, Jean-Philippe Pin
Antibodies have enormous therapeutic and biotechnology potential. G protein-coupled receptors (GPCRs), the main targets in drug development, are of major interest in antibody development programs. Metabotropic glutamate receptors are dimeric GPCRs that can control synaptic activity in a multitude of ways. Here we identify llama nanobodies that specifically recognize mGlu2 receptors, among the eight subtypes of mGluR subunits. Among these nanobodies, DN10 and 13 are positive allosteric modulators (PAM) on homodimeric mGlu2, while DN10 displays also a significant partial agonist activity...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29207276/environmental-enrichment-improves-hippocampal-function-in-aged-rats-by-enhancing-learning-and-memory-ltp-and-mglur5-homer1c-activity
#5
Guiseppe P Cortese, Andrew Olin, Kenneth O'Riordan, Rikki Hullinger, Corinna Burger
Previous studies from our laboratory have shown that environmental enrichment (EE) in young rats results in improved learning ability and enhanced metabotropic glutamate receptor-dependent long-term potentiation (mGluR-dependent LTP) resulting from sustained activation of p70S6 kinase. Here, we investigated whether 1-month EE is sufficient to improve hippocampus-dependent learning and memory and enhance hippocampal LTP in 23-24 month-old Fischer 344 male rats. Aged rats were housed in environmentally enriched, socially enriched, or standard housing conditions...
November 16, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29203851/dynamic-landscape-of-the-local-translation-at-activated-synapses
#6
T M Khlebodarova, V V Kogai, E A Trifonova, V A Likhoshvai
The mammalian target of rapamycin (mTOR) signaling pathway is the central regulator of cap-dependent translation at the synapse. Disturbances in mTOR pathway have been associated with several neurological diseases, such as autism and epilepsy. RNA-binding protein FMRP, a negative regulator of translation initiation, is one of the key components of the local translation system. Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and dephosphorylation by PP2A phosphatase, respectively...
December 5, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29195167/effects-of-short-and-long-term-aripiprazole-treatment-on-group-i-mglurs-in-the-nucleus-accumbens-comparison-with-haloperidol
#7
Jeremy S Lum, Bo Pan, Chao Deng, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
The D2 receptor partial agonist, aripiprazole, has shown increased therapeutic efficacy for schizophrenia, autism and Tourette's syndrome compared to traditional antipsychotics such as the D2 receptor antagonist, haloperidol. Recent evidence suggests this superior profile may be associated with downstream effects on glutamatergic synapses. Group 1 metabotropic glutamate receptors (mGluRs) and their endogenous modulators, Norbin and Homer1, are regulated by D2 receptor activity, particularly within the nucleus accumbens (NAc), a target region of aripiprazole and haloperidol...
November 21, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29176838/inhibition-of-group-i-metabotropic-glutamate-receptors-protects-against-prion-toxicity
#8
Despoina Goniotaki, Asvin K K Lakkaraju, Amulya N Shrivastava, Pamela Bakirci, Silvia Sorce, Assunta Senatore, Rajlakshmi Marpakwar, Simone Hornemann, Fabrizio Gasparini, Antoine Triller, Adriano Aguzzi
Prion infections cause inexorable, progressive neurological dysfunction and neurodegeneration. Expression of the cellular prion protein PrPC is required for toxicity, suggesting the existence of deleterious PrPC-dependent signaling cascades. Because group-I metabotropic glutamate receptors (mGluR1 and mGluR5) can form complexes with the cellular prion protein (PrPC), we investigated the impact of mGluR1 and mGluR5 inhibition on prion toxicity ex vivo and in vivo. We found that pharmacological inhibition of mGluR1 and mGluR5 antagonized dose-dependently the neurotoxicity triggered by prion infection and by prion-mimetic anti-PrPC antibodies in organotypic brain slices...
November 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29173281/akt-isoforms-have-distinct-hippocampal-expression-and-roles-in-synaptic-plasticity
#9
Josien Levenga, Helen Wong, Ryan A Milstead, Bailey N Keller, Lauren E LaPlante, Charles A Hoeffer
AKT is a kinase regulating numerous cellular processes in the brain and mutations in AKT are known to affect brain function. AKT is indirectly implicated in synaptic plasticity, but its direct role has not been studied. Moreover, three highly related AKT isoforms are expressed in the brain, but their individual roles are poorly understood. We find in Mus musculus, each AKT isoform has a unique expression pattern in the hippocampus, with AKT1 and AKT3 primarily in neurons but displaying local differences, while AKT2 is in astrocytes...
November 27, 2017: ELife
https://www.readbyqxmd.com/read/29163124/the-search-for-an-effective-therapy-to-treat-fragile-x-syndrome-dream-or-reality
#10
REVIEW
Sara Castagnola, Barbara Bardoni, Thomas Maurin
Fragile X Syndrome (FXS) is the most common form of intellectual disability and a primary cause of autism. It originates from the lack of the Fragile X Mental Retardation Protein (FMRP), which is an RNA-binding protein encoded by the Fragile X Mental Retardation Gene 1 (FMR1) gene. Multiple roles have been attributed to this protein, ranging from RNA transport (from the nucleus to the cytoplasm, but also along neurites) to translational control of mRNAs. Over the last 20 years many studies have found a large number of FMRP mRNA targets, but it is still not clear which are those playing a critical role in the etiology of FXS...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/29163080/behavioral-and-neurochemical-phenotyping-of-mice-incapable-of-homer1a-induction
#11
Michael C Datko, Jia-Hua Hu, Melanie Williams, Cindy M Reyes, Kevin D Lominac, Georg von Jonquieres, Matthias Klugmann, Paul F Worley, Karen K Szumlinski
Immediate early and constitutively expressed products of the Homer1 gene regulate the functional assembly of post-synaptic density proteins at glutamatergic synapses to influence excitatory neurotransmission and synaptic plasticity. Earlier studies of Homer1 gene knock-out (KO) mice indicated active, but distinct, roles for IEG and constitutively expressed Homer1 gene products in regulating cognitive, emotional, motivational and sensorimotor processing, as well as behavioral and neurochemical sensitivity to cocaine...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/29142061/effects-of-regulatory-bc1-rna-deletion-on-synaptic-plasticity-learning-and-memory
#12
Ain Chung, Nessy Dahan, Juan Marcos Alarcon, André A Fenton
Nonprotein coding dendritic BC1 RNA regulates translation of mRNAs in neurons. We examined two lines of BC1 knockout mice and report that loss of BC1 RNA exaggerates group I mGluR-stimulated LTD of the Schaffer collateral synapse, with one of the lines showing a much more enhanced DHPG-induced LTD than the other. When the animals were given the hippocampus-synaptic plasticity-dependent active place avoidance task, learning and memory were impaired in the BC1-KO line with the more severely altered DHPG-induced LTD...
December 2017: Learning & Memory
https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#13
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29114037/reducing-eif4e-eif4g-interactions-restores-the-balance-between-protein-synthesis-and-actin-dynamics-in-fragile-x-syndrome-model-mice
#14
Emanuela Santini, Thu N Huynh, Francesco Longo, So Yeon Koo, Edward Mojica, Laura D'Andrea, Claudia Bagni, Eric Klann
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and autism spectrum disorder. FXS is caused by silencing of the FMR1 gene, which encodes fragile X mental retardation protein (FMRP), an mRNA-binding protein that represses the translation of its target mRNAs. One mechanism by which FMRP represses translation is through its association with cytoplasmic FMRP-interacting protein 1 (CYFIP1), which subsequently sequesters and inhibits eukaryotic initiation factor 4E (eIF4E). CYFIP1 shuttles between the FMRP-eIF4E complex and the Rac1-Wave regulatory complex, thereby connecting translational regulation to actin dynamics and dendritic spine morphology, which are dysregulated in FXS model mice that lack FMRP...
November 7, 2017: Science Signaling
https://www.readbyqxmd.com/read/29102027/effect-of-novel-allosteric-modulators-of-metabotropic-glutamate-receptors-on-drug-self-administration-and-relapse-a-review-of-preclinical-studies-and-their-clinical-implications
#15
REVIEW
Daniele Caprioli, Zuzana Justinova, Marco Venniro, Yavin Shaham
Results from preclinical rodent studies during the last 20 years implicated glutamate neurotransmission in different brain regions in drug self-administration and rodent models of relapse. These results, along with evidence for drug-induced neuroadaptations in glutamatergic neurons and receptors, suggested that addiction might be treatable by medications that inhibit glutamatergic responses to drugs of abuse, drug-associated cues, and stressors. This idea is supported by findings in rodent and primate models that drug self-administration and relapse are reduced by systemic injections of antagonists of ionotropic glutamate receptors or metabotropic glutamate receptors (mGluRs) or orthosteric agonists of mGluR2/3...
September 5, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29074619/presynaptic-mglur5-receptor-controls-glutamatergic-input-through-protein-kinase-c-nmda-receptors-in-paclitaxel-induced-neuropathic-pain
#16
Jing-Dun Xie, Shao-Rui Chen, Hui-Lin Pan
Chemotherapeutic drugs such as paclitaxel cause painful peripheral neuropathy in many cancer patients and survivors. Although NMDA receptors (NMDARs) at primary afferent terminals are known to be critically involved in chemotherapy-induced chronic pain, the upstream signaling mechanism that leads to presynaptic NMDAR activation is unclear. Group I metabotropic glutamate receptors (mGluRs) play a role in synaptic plasticity and NMDAR regulation. Here we report that the Group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) significantly increased the frequency of miniature excitatory postsynaptic currents (EPSCs) and the amplitude of monosynaptic EPSCs evoked from the dorsal root...
October 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29071990/-effect-of-electroacupuncture-intervention-on-expression-of-synaptic-plasticity-related-molecules-in-amygdala-in-chronic-pain-negative-affection-rats
#17
Cheng-Lin Duanmu, Xiu-Mei Feng, Ya-Xia Yan, Jun-Ying Wang, Yong-Hui Gao, Li-Na Qiao, Shu-Ping Chen, Jian-Liang Zhang, Jun-Ling Liu
OBJECTIVE: To observe the effect of electroacupuncture (EA) on expression of synaptic plasticity-related glutamate N-methyl-D-aspartate (NMDA) receptor subunit NR 1, gamma-aminobutyric acid (GABA) receptor subunits (Aβ 2, B 1), etc. in the amygdala in chronic neuropathic pain negative affection (CNPPNA) rats, so as to reveal its mechanism underlying pain relief. METHODS: Male Wistar rats were randomized into normal control, CNPPNA model, EA, and anesthesia+EA (AEA)groups (n=14 in each group, 8 for quantitative RT-PCR and 6 for immunofluorescence staining)...
February 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29025923/plasticity-of-signaling-by-spinal-estrogen-receptor-alpha-kappa-opioid-receptor-and-mglurs-over-the-rat-reproductive-cycle-regulates-spinal-endomorphin-2-antinociception-relevance-of-endogenous-biased-agonism
#18
Nai-Jiang Liu, Vijaya Murugaiyan, Emiliya M Storman, Stephen A Schnell, Arjun Kumar, Martin W Wessendorf, Alan R Gintzler
We previously showed that intrathecal application of endomorphin 2 [EM2; the highly specific endogenous mu-opioid receptor (MOR) ligand] induces antinociception that varies with stage of the rat estrous cycle -- minimal during diestrus and prominent during proestrus. Earlier studies, however, did not identify proestrus-activated signaling strategies that enable spinal EM2 antinociception. We now report that in female rats, increased spinal dynorphin release and kappa-opioid receptor (KOR) signaling, as well as the emergence of glutamate-activated mGluR1 signaling, are critical to the transition from an EM2 non-responsive (during diestrus) to an analgesically responsive state (during proestrus)...
October 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29024451/activation-of%C3%A2-group-ii-metabotropic-glutamate-receptors-increases-proliferation-but-does-not-influence-neuronal-differentiation-of-a-human-neural-stem-cell-line
#19
Anne Dindler, Morten Blaabjerg, Morad Kamand, Helle Bogetofte, Morten Meyer
The multiple functions of glutamate include regulation of neural development and stem cells. While the importance of the ionotropic glutamate receptors is well established, less is known about the role of metabotropic glutamate receptors (mGluRs). In this study, we examined the effects of pharmacological activation and inhibition of mGluR2/3 on proliferation, differentiation and viability of a human neural stem cell line. Immunofluorescence staining revealed the presence of mGluR2/3 receptors on both proliferating and differentiating stem cells, including cells differentiated into β-tubulin III-positive immature neurons and glial fibrillary acidic protein-positive astrocytes...
October 11, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29022871/a-postmortem-analysis-of-nmda-ionotropic-and-group-1-metabotropic-glutamate-receptors-in-the-nucleus-accumbens-in-schizophrenia
#20
Jeremy S Lum, Samuel J Millard, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
BACKGROUND: The nucleus accumbens (NAcc) has been implicated in the pathology and treatment of schizophrenia. Recent postmortem evidence suggests a hyperglutamatergic state in the NAcc. With the present study we aimed to explore possible glutamatergic alterations in the NAcc of a large schizophrenia cohort. METHODS: We performed immunoblots on postmortem NAcc samples from 30 individuals who had schizophrenia and 30 matched controls. We examined the protein expression of primary glutamatergic receptors, including the N-methyl-D-aspartate (NMDA) receptor (NR1, NR2A and NR2B subunits) and the group 1 metabotropic glutamate receptor (mGluR1 and mGluR5; dimeric and monomeric forms)...
October 6, 2017: Journal of Psychiatry & Neuroscience: JPN
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