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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/29016848/mdm2-mediates-fmrp-and-gp1-mglur-dependent-protein-translation-and-neural-network-activity
#4
Dai-Chi Liu, Joseph Seimetz, Kwan Young Lee, Auinash Kalsotra, Hee Jung Chung, Hua Lu, Nien-Pei Tsai
Activating Group 1 (Gp1) metabotropic glutamate receptors (mGluRs), including mGluR1 and mGluR5, elicits translation-dependent neural plasticity mechanisms that are crucial to animal behavior and circuit development. Dysregulated Gp1 mGluR signaling has been observed in numerous neurological and psychiatric disorders. However, the molecular pathways underlying Gp1 mGluR-dependent plasticity mechanisms are complex and have been elusive. In this study, we identified a novel mechanism through which Gp1 mGluR mediates protein translation and neural plasticity...
October 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28969983/roles-for-arc-in-metabotropic-glutamate-receptor-dependent-ltd-and-synapse-elimination-implications-in-health-and-disease
#5
REVIEW
Julia R Wilkerson, Joseph P Albanesi, Kimberly M Huber
The Arc gene is robustly transcribed in specific neural ensembles in response to experience-driven activity. Upon induction, Arc mRNA is transported to dendrites, where it can be rapidly and locally translated by activation of metabotropic glutamate receptors (mGluR1/5). mGluR-induced dendritic synthesis of Arc is implicated in weakening or elimination of excitatory synapses by triggering endocytosis of postsynaptic AMPARs in both hippocampal CA1 and cerebellar Purkinje neurons. Importantly, CA1 neurons with experience-induced Arc mRNA are susceptible, or primed for mGluR-induced long-term synaptic depression (mGluR-LTD)...
September 29, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28962849/the-expression-of-select-genes-necessary-for-membrane-associated-estrogen-receptor-signaling-differ-by-sex-in-adult-rat-hippocampus
#6
John Meitzen, Kyla A Britson, Krista Tuomela, Paul G Mermelstein
17β-estradiol can rapidly modulate neuron function via membrane estrogen receptors (ERs) in a sex-specific manner. For example, female rat hippocampal neurons express palmitoylated versions of ERα and ERβ that associate with the plasma membrane. These membrane-associated ERs are organized by caveolin proteins into functional signaling microdomains with metabotropic glutamate receptors (mGluRs). ER/mGluR signaling mediates several sex-specific estradiol actions on hippocampal neuron function. An important unanswered question regards the mechanism by which sex-specific membrane-associated ER signaling is generated, especially since it has been previously demonstrated that mGluR action is not sex-specific...
September 26, 2017: Steroids
https://www.readbyqxmd.com/read/28948209/an-essential-role-of-fyn-in-the-modulation-of-metabotropic-glutamate-receptor-1-in-neurons
#7
Dao-Zhong Jin, Li-Min Mao, John Q Wang
Fyn is a member of the Src family of nonreceptor tyrosine kinases and is broadly expressed in the CNS. As a synapse-enriched kinase, Fyn interacts with and phosphorylates local substrates to regulate synaptic transmission and plasticity, although our knowledge of specific targets of Fyn at synaptic sites remains incomplete and the accurate role of Fyn in regulating synaptic proteins is poorly understood. In this study, we initiated an effort to explore the interaction of Fyn with a metabotropic glutamate receptor (mGluR)...
July 2017: ENeuro
https://www.readbyqxmd.com/read/28943283/step-inhibition-reverses-behavioral-electrophysiologic-and-synaptic-abnormalities-in-fmr1-ko-mice
#8
Manavi Chatterjee, Pradeep K Kurup, Camilla J Lundbye, Anna Karina Hugger Toft, Jeemin Kwon, Jessie Benedict, Marija Kamceva, Tue G Banke, Paul J Lombroso
Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability, with additional symptoms including attention deficit and hyperactivity, anxiety, impulsivity, and repetitive movements or actions. The majority of FXS cases are attributed to a CGG expansion that leads to transcriptional silencing and diminished expression of fragile X mental retardation protein (FMRP). FMRP, an RNA binding protein, regulates the synthesis of dendritically-translated mRNAs by stalling ribosomal translation. Loss of FMRP leads to increased translation of some of these mRNAs, including the CNS-specific tyrosine phosphatase STEP (STriatal-Enriched protein tyrosine Phosphatase)...
September 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28935587/glutamatergic-synapses-in-neurodevelopmental-disorders
#9
REVIEW
Edoardo Moretto, Luca Murru, Giuseppe Martano, Jenny Sassone, Maria Passafaro
Neurodevelopmental disorders (NDDs) are a group of diseases whose symptoms arise during childhood or adolescence and that impact several higher cognitive functions such as learning, sociability and mood. Accruing evidence suggests that a shared pathogenic mechanism underlying these diseases is the dysfunction of glutamatergic synapses. We summarize present knowledge on autism spectrum disorders (ASD), intellectual disability (ID), Down syndrome (DS), Rett syndrome (RS) and attention-deficit hyperactivity disorder (ADHD), highlighting the involvement of glutamatergic synapses and receptors in these disorders...
September 19, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28935545/integrated-molecular-analysis-of-tamoxifen-resistant-invasive-lobular-breast-cancer-cells-identifies-mapk-and-grm-mglur-signaling-as-therapeutic-vulnerabilities
#10
REVIEW
Hillary Stires, Mary M Heckler, Xiaoyong Fu, Zhao Li, Catherine S Grasso, Michael J Quist, Joseph A Lewis, Uwe Klimach, Alan Zwart, Akanksha Mahajan, Balázs Győrffy, Luciane R Cavalli, Rebecca B Riggins
Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC cell model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes...
September 19, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28882644/postsynaptic-n-type-or-p-q-type-calcium-channels-mediate-long-term-potentiation-by-group-i-metabotropic-glutamate-receptors-in-the-trigeminal-oralis
#11
Haein Weon, Tae Wan Kim, Dong-Ho Youn
AIMS: Both N-type and P/Q-type voltage-gated Ca(2+) channels (VGCCs) are involved in the induction of long-term potentiation (LTP), the long-lasting increase of synaptic strength, in the central nervous system. To provide further information on the roles of N-type and P/Q-type VGCCs in the induction of LTP at excitatory synapses of trigeminal primary afferents in the spinal trigeminal subnucleus oralis (Vo), we investigated whether they contribute to the induction of LTP by activation of group I metabotropic glutamate receptors (mGluRs)...
November 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28838696/synthesis-and-optimization-of-4-5-6-7-tetrahydrooxazolo-4-5-c-pyridines-as-potent-and-orally-active-metabotropic-glutamate-receptor-5-negative-allosteric-modulators
#12
Wataru Hirose, Yoshihiro Kato, Itaru Natsutani, Makoto Takata, Maiko Kitaichi, Satoki Imai, Shun Hayashi, Yukiyo Arai, Kohei Hoshino, Kohzo Yoshida
We describe here the design, synthesis and characterization of a series of 4,5,6,7-tetrahydrooxazolo[4,5-c]pyridines as metabotropic glutamate receptor (mGluR) 5 negative allosteric modulators (NAMs). Optimization of the substituents led to the identification of several compounds with good pharmacokinetic profiles, including long half life and high oral bioavailability, in both rats and monkeys. The receptor occupancy test in the rat cortex revealed favorable brain penetration of these compounds. The reprsentative compound 13 produced oral antidepressant-like effect in the rat forced swimming test (MED: 0...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28831099/unilateral-stimulation-of-the-lateral-division-of-the-dorsal-telencephalon-induces-synaptic-plasticity-in-the-bilateral-medial-division-of-zebrafish
#13
Yao-Ju Wu, Yu-Lan Chen, Tso-Hao Tang, Ming-Chong Ng, Tamara G Amstislavskaya, Maria A Tikhonova, Yi-Ling Yang, Kwok-Tung Lu
This study was aimed to evaluate the synaptic plasticity in projections from the dorsal lateral region (Dl) to the bilateral dorsal medial region (Dm) of the zebrafish telencephalon. The results showed that unilateral electrical stimulation of the Dl evokes a negative field potential (FP) in both the contralateral and ipsilateral side of the Dm. We tested synaptic plasticity, including high-frequency stimulation-induced LTP (HFS-LTP) and low-frequency stimulation-induced LTD (LFS-LTD). We demonstrated that HFS-induced bilateral LTP is NMDAR-dependent by the application of an NMDAR antagonist, DL-AP5 (30 μM, suprafused for 10 min), which blocked the HFS-induced LTP in both the contralateral and ipsilateral Dm...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28829739/allosteric-control-of-an-asymmetric-transduction-in-a-g-protein-coupled-receptor-heterodimer
#14
Junke Liu, Zongyong Zhang, David Moreno-Delgado, James Ar Dalton, Xavier Rovira, Ana Trapero, Cyril Goudet, Amadeu Llebaria, Jesús Giraldo, Qilin Yuan, Philippe Rondard, Siluo Huang, Jianfeng Liu, Jean-Philippe Pin
GPCRs play critical roles in cell communication. Although GPCRs can form heteromers, their role in signaling remains elusive. Here we used rat metabotropic glutamate (mGlu) receptors as prototypical dimers to study the functional interaction between each subunit. mGluRs can form both constitutive homo- and heterodimers. Whereas both mGlu2 and mGlu4 couple to G proteins, G protein activation is mediated by mGlu4 heptahelical domain (HD) exclusively in mGlu2-4 heterodimers. Such asymmetric transduction results from the action of both the dimeric extracellular domain, and an allosteric activation by the partially-activated non-functional mGlu2 HD...
August 10, 2017: ELife
https://www.readbyqxmd.com/read/28822034/microrna-expression-target-genes-and-signaling-pathways-in-infants-with-a-ventricular-septal-defect
#15
Hui Chai, Zhaoyuan Yan, Ke Huang, Yuanqing Jiang, Lin Zhang
This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively...
August 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28821679/upf1-governs-synaptic-plasticity-through-association-with-a-stau2-rna-granule
#16
Tyson E Graber, Erika Freemantle, Mina N Anadolu, Sarah Hébert-Seropian, Robyn L MacAdam, Unkyung Shin, Huy-Dung Hoang, Tommy Alain, Jean-Claude Lacaille, Wayne S Sossin
Neuronal mRNAs can be packaged in reversibly stalled polysome granules before their transport to distant synaptic locales. Stimulation of synaptic metabotropic glutamate receptors (mGluRs) reactivates translation of these particular mRNAs to produce plasticity-related protein; a phenomenon exhibited during mGluR-mediated LTD. This form of plasticity is deregulated in Fragile X Syndrome, a monogenic form of autism in humans, and understanding the stalling and reactivation mechanism could reveal new approaches to therapies...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821676/brief-novel-visual-experience-fundamentally-changes-synaptic-plasticity-in-the-mouse-visual-cortex
#17
Shuo Li, Laijian Wang, Xiaoxiu Tie, Kazuhiro Sohya, Xian Lin, Alfredo Kirkwood, Bin Jiang
LTP has been known to be a mechanism by which experience modifies synaptic responses in the neocortex. Visual deprivation in the form of dark exposure or dark rearing from birth enhances NMDAR-dependent LTP in layer 2/3 of visual cortex, a process often termed metaplasticity, which may involve changes in NMDAR subunit composition and function. However, the effects of reexposure to light after dark rearing from birth on LTP induction have not been explored. Here, we showed that the light exposure after dark rearing revealed a novel NMDAR independent form of LTP in the layer 2/3 pyramidal cells in visual cortex of mice of both sexes, which is dependent on mGluR5 activation and is associated with intracellular Ca(2+) rise, CaMKII activity, PKC activity, and intact protein synthesis...
September 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28813782/urea-cycle-pathway-targeted-therapeutic-action-of-naringin-against-ammonium-chloride-induced-hyperammonemic-rats
#18
Arumugam Ramakrishnan, Natesan Vijayakumar
Ammonia is a well-known neurotoxin that causes liver disease and urea cycle disorder. Excessive ammonia content in the blood leads to hyperammonemic condition and affects both excitatory and inhibitory neurotransmission including brain edema and coma. Naringin, a plant bioflavonoid present in various citrus fruits and mainly extracted from the grape fruit. This study was designed to assess the protective effect of naringin on ammonium chloride (NH4Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitoneal injections (i...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28800512/metabotropic-glutamate-receptors-as-emerging-research-targets-in-bipolar-disorder
#19
REVIEW
Caren J Blacker, Charles P Lewis, Mark A Frye, Marin Veldic
Glutamatergic dysregulation is implicated in the neuropathology of bipolar disorder (BD). There is increasing interest in investigating the role of metabotropic glutamate receptors (mGluRs) in BD and as a target for treatment intervention. Bipolar mGluR studies (published January 1992-April 2016) were identified via PubMed, Embase, Web of Science, and Scopus. Full-text screening, data extraction, and quality appraisal were conducted in duplicate, with strict inclusion and exclusion criteria. The initial literature search for mGluRs in BD, including non-bipolar mood disorders and primary psychotic disorders, identified 1544 articles...
July 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28772121/cell-type-specific-translation-profiling-reveals-a-novel-strategy-for-treating-fragile-x-syndrome
#20
Sophie R Thomson, Sang S Seo, Stephanie A Barnes, Susana R Louros, Melania Muscas, Owen Dando, Caoimhe Kirby, David J A Wyllie, Giles E Hardingham, Peter C Kind, Emily K Osterweil
Excessive mRNA translation downstream of group I metabotropic glutamate receptors (mGlu1/5) is a core pathophysiology of fragile X syndrome (FX); however, the differentially translating mRNAs that contribute to altered neural function are not known. We used translating ribosome affinity purification (TRAP) and RNA-seq to identify mistranslating mRNAs in CA1 pyramidal neurons of the FX mouse model (Fmr1(-/y)) hippocampus, which exhibit exaggerated mGlu1/5-induced long-term synaptic depression (LTD). In these neurons, we find that the Chrm4 transcript encoding muscarinic acetylcholine receptor 4 (M4) is excessively translated, and synthesis of M4 downstream of mGlu5 activation is mimicked and occluded...
August 2, 2017: Neuron
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