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https://www.readbyqxmd.com/read/28419871/short-term-inhibition-of-gabaergic-ipscs-induced-by-association-of-pre-and-postsynaptic-activation-in-the-neonatal-hippocampus
#1
Megumi Taketo, Hiroko Matsuda
Activity-dependent plasticity including short and long-term depression accompanied by a reduction in transmitter release probability has been demonstrated in both inhibitory and excitatory synapses. In the neonatal hippocampus, repetitive postsynaptic depolarization is followed by presynaptic alterations of the efficacy of GABAAergic transmission. Both facilitation and inhibition have been observed, but the mechanisms underlying this plasticity have not yet been elucidated. In the present experiment, repetitive postsynaptic depolarization by itself did not cause marked alterations of spontaneous inhibitory postsynaptic currents (sIPSCs)...
April 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28417952/investigating-the-molecular-mechanism-of-positive-and-negative-allosteric-modulators-in-the-calcium-sensing-receptor-dimer
#2
Stine Engesgaard Jacobsen, Ulrik Gether, Hans Bräuner-Osborne
Allosteric modulators that are targeting the calcium-sensing receptor (CaSR) hold great therapeutic potential, and elucidating the molecular basis for modulation would thus benefit the development of novel therapeutics. In the present study, we aimed at investigating the mechanism of allosteric modulation in CaSR by testing dimers carrying mutations in the allosteric site of one or both of the subunits. To ensure measurements on a well-defined dimer composition, we applied a trans-activation system in which only the specific heterodimer of two loss-of-function mutants responded to agonist...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28413831/differential-ability-of-the-dorsal-and-ventral-rat-hippocampus-to-exhibit-group-i-metabotropic-glutamate-receptor-dependent-synaptic-and-intrinsic-plasticity
#3
Patrick Tidball, Hannah V Burn, Kai Lun Teh, Arturas Volianskis, Graham L Collingridge, Stephen M Fitzjohn
BACKGROUND: The hippocampus is critically involved in learning and memory processes. Although once considered a relatively homogenous structure, it is now clear that the hippocampus can be divided along its longitudinal axis into functionally distinct domains, responsible for the encoding of different types of memory or behaviour. Although differences in extrinsic connectivity are likely to contribute to this functional differentiation, emerging evidence now suggests that cellular and molecular differences at the level of local hippocampal circuits may also play a role...
January 2017: Brain Neurosci Adv
https://www.readbyqxmd.com/read/28396447/dual-optical-control-and-mechanistic-insights-into-photoswitchable-group-ii-and-iii-metabotropic-glutamate-receptors
#4
Joshua Levitz, Johannes Broichhagen, Philipp Leippe, David Konrad, Dirk Trauner, Ehud Y Isacoff
G protein-coupled receptor (GPCR) signaling occurs in complex spatiotemporal patterns that are difficult to probe using standard pharmacological and genetic approaches. A powerful approach for dissecting GPCRs is to use light-controlled pharmacological agents that are tethered covalently and specifically to genetically engineered receptors. However, deficits in our understanding of the mechanism of such photoswitches have limited application of this approach and its extension to other GPCRs. In this study, we have harnessed the power of bioorthogonal tethering to SNAP and CLIP protein tags to create a family of light-gated metabotropic glutamate receptors (mGluRs)...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28395974/antidepressant-like-activity-of-icariin-mediated-by-group-i-mglurs-in-prenatally-stressed-offspring
#5
Xiaoxiao Zhang, Hongli Sun, Qian Su, Tianwei Lin, Huiping Zhang, Junli Zhang, Shaokang Dang, Zhongliang Zhu
OBJECTIVE: The present study was performed to identify antidepressant-like activity of icariin in prenatally stressed male rats. METHODS: The effects of icariin on PRS-induced depression were examined using sucrose preference test (SPT) and forced swimming test (FST) in male offspring, and measuring protein and mRNA expressions of group I mGluRs receptors and EAAT2 via western blotting and quantitative real-time PCR assays. RESULTS: The results indicated that prenatal restraint stress (PRS) resulted in several behavioral anomalies...
April 7, 2017: Brain & Development
https://www.readbyqxmd.com/read/28393639/the-safety-of-extended-release-drug-formulations-for-the-treatment-of-adhd
#6
Ann Childress
Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder affecting millions of patients worldwide. Effective treatments have been available for more than 60 years in the form of immediate-release (IR) stimulants However, stimulants have a high risk for abuse and are associated with adverse effects Including elevated blood pressure and heart rate, insomnia and decreased appetite. IR formulations also require multiple daily dosing. The search for improved safety, tolerability and convenience has led to the development of multiple extended-release (ER) stimulant and non-stimulant formulations...
April 10, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28392297/group-ii-metabotropic-glutamate-receptor-interactions-with-nherf-scaffold-proteins-implications-for-receptor-localization-in-brain
#7
Stefanie L Ritter-Makinson, Maryse Paquet, James W Bogenpohl, Rachel E Rodin, C Chris Yun, Edward J Weinman, Yoland Smith, Randy A Hall
The group II metabotropic glutamate receptors mGluR2 and mGluR3 are key modulators of glutamatergic neurotransmission. In order to identify novel Group II metabotropic glutamate receptor (mGluR)-interacting partners, we screened the C-termini of mGluR2 and mGluR3 for interactions with an array of PDZ domains. These screens identified the Na+/H+ exchanger regulatory factors 1 and 2 (NHERF-1 & -2) as candidate interacting partners. Follow-up co-immunoprecipitation studies demonstrated that both mGluR2 and mGluR3 can associate with NHERF-1 and NHERF-2 in a cellular context...
April 7, 2017: Neuroscience
https://www.readbyqxmd.com/read/28369952/a-calcium-dependent-pathway-underlies-activity-dependent-plasticity-of-electrical-synapses-in-the-thalamic-reticular-nucleus
#8
Jessica Sevetson, Sarah Fittro, Emily Heckman, Julie S Haas
Recent results have demonstrated modification of electrical synapse strength by varied forms of neuronal activity. However, the mechanisms underlying plasticity induction in central mammalian neurons are unclear. Here we show that the two established inductors of plasticity at electrical synapses in the thalamic reticular nucleus - paired burst spiking in coupled neurons, and mGluR-dependent tetanization of synaptic input - are separate pathways that converge at a common downstream endpoint. Using occlusion experiments and pharmacology in patched pairs of coupled neurons in vitro, we show that burst-induced depression depends on calcium entry via voltage-gated channels, is blocked by BAPTA chelation, and recruits intracellular calcium release on its way to activation of phosphatase activity...
March 29, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28369311/control-of-glutamate-transport-by-extracellular-potassium-basis-for-a-negative-feedback-on-synaptic-transmission
#9
Theresa S Rimmele, Anne-Bérengère Rocher, Joel Wellbourne-Wood, Jean-Yves Chatton
Glutamate and K+, both released during neuronal firing, need to be tightly regulated to ensure accurate synaptic transmission. Extracellular glutamate and K+ ([K+]o) are rapidly taken up by glutamate transporters and K+-transporters or channels, respectively. Glutamate transport includes the exchange of one glutamate, 3 Na+, and one proton, in exchange for one K+. This K+ efflux allows the glutamate binding site to reorient in the outwardly facing position and start a new transport cycle. Here, we demonstrate the sensitivity of the transport process to [K+]o changes...
March 25, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28365868/metabotropic-glutamate-receptors-protect-oligodendrocytes-from-acute-ischemia-in-the-mouse-optic-nerve
#10
Arthur M Butt, Ilaria Vanzulli, Maria Papanikolaou, Irene Chacon De La Rocha, Virginia E Hawkins
Studies by Bruce Ransom and colleagues have made a major contribution to show that white matter is susceptible to ischemia/hypoxia. White matter contains axons and the glia that support them, notably myelinating oligodendrocytes, which are highly vulnerable to ischemic-hypoxic damage. Previous studies have shown that metabotropic GluRs (mGluRs) are cytoprotective for oligodendrocyte precursor cells and immature oligodendrocytes, but their potential role in adult white matter was unresolved. Here, we report that group 1 mGluR1/5 and group 2 mGluR3 subunits are expressed in optic nerves from mice aged postnatal day (P)8-12 and P30-35...
April 1, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28363980/a-presynaptic-group-iii-mglur-recruits-g%C3%AE-%C3%AE-snare-interactions-to-inhibit-synaptic-transmission-by-cone-photoreceptors-in-the-vertebrate-retina
#11
Matthew J Van Hook, Norbert Babai, Zack Zurawski, Yun Young Yim, Heidi E Hamm, Wallace B Thoreson
G-protein βγ subunits (Gβγ) interact with presynaptic proteins and regulate neurotransmitter release downstream of Ca(2+) influx. To accomplish their roles in sensory signaling, photoreceptor synapses employ specialized presynaptic proteins that support neurotransmission at active zone structures known as ribbons. While several G-protein coupled receptors (GPCRs) influence synaptic transmission at ribbon synapses of cones and other retinal neurons, it is unknown whether Gβγ contributes to these effects...
March 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28337539/homer1-vesl-1-in-the-rat-esophagus-focus-on-myenteric-plexus-and-neuromuscular-junction
#12
J Zimmermann, W L Neuhuber, M Raab
Homer1, a scaffolding protein of the postsynaptic density (PSD), enriched at excitatory synapses is known to anchor and modulate group I metabotropic glutamate receptors (mGluRs) and different channel- and receptor-proteins. Homer proteins are expressed in neurons of different brain regions, but also in non-neuronal tissues like skeletal muscle. Occurrence and location of Homer1 and mGluR5 in myenteric plexus and neuromuscular junctions (NMJ) of rat esophagus have yet not been characterized. We located Homer1 and mGluR5 immunoreactivity (-iry) in rat esophagus and focused on myenteric neurons, intraganglionic laminar endings (IGLEs) and NMJs, using double- and triple-label immunohistochemistry and confocal laser scanning microscopy...
March 23, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28335551/molecular-basis-for-modulation-of-metabotropic-glutamate-receptors-and-their-drug-actions-by-extracellular-ca-2
#13
REVIEW
Juan Zou, Jason Y Jiang, Jenny J Yang
Metabotropic glutamate receptors (mGluRs) associated with the slow phase of the glutamatergic signaling pathway in neurons of the central nervous system have gained importance as drug targets for chronic neurodegenerative diseases. While extracellular Ca(2+) was reported to exhibit direct activation and modulation via an allosteric site, the identification of those binding sites was challenged by weak binding. Herein, we review the discovery of extracellular Ca(2+) in regulation of mGluRs, summarize the recent developments in probing Ca(2+) binding and its co-regulation of the receptor based on structural and biochemical analysis, and discuss the molecular basis for Ca(2+) to regulate various classes of drug action as well as its importance as an allosteric modulator in mGluRs...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28326936/a-role-for-the-locus-coeruleus-in-the-analgesic-efficacy-of-n-acetylaspartylglutamate-peptidase-gcpii-inhibitors-zj43-and-2-pmpa
#14
Takahiro Nonaka, Toshihiko Yamada, Tatsuhiro Ishimura, Daiying Zuo, John R Moffett, Joseph H Neale, Tatsuo Yamamoto
N-acetylaspartylglutamate (NAAG) is the third most prevalent and widely distributed neurotransmitter in the mammalian nervous system. NAAG activates a group II metabotropic glutamate receptor (mGluR3) and is inactivated by an extracellular enzyme, glutamate carboxypeptidase II (GCPII) in vivo. Inhibitors of this enzyme are analgesic in animal models of inflammatory, neuropathic and bone cancer pain. NAAG and GCPII are present in the locus coeruleus, a center for the descending noradrenergic inhibitory pain system...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28322866/decreased-anxiety-voluntary-ethanol-intake-and-ethanol-induced-cpp-acquisition-following-activation-of-the-metabotropic-glutamate-receptor-8-mglur8
#15
Amine Bahi
Metabotropic glutamate receptors (mGluRs) are important modulators of excitatory neurotransmission, and have been implicated in addiction to alcohol and anxiety-related behaviors. However, the behavioral consequence and contribution of individual subtypes are not known yet. This study determined the effects of mGluR8 activation on anxiety-like behavior, voluntary ethanol intake and ethanol-induced conditioned reward. To this aim, anxiety and spontaneous behavior were measured in C57BL/6J mice using the elevated plus maze (EPM), open field (OF) and light-dark box (LDB) tests after systemic injection of the selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine ((S)-3,4-DCPG)...
March 18, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28322276/identifying-fast-onset-antidepressants-using-rodent-models
#16
M J Ramaker, S C Dulawa
Depression is a leading cause of disability worldwide and a major contributor to the burden of suicide. A major limitation of classical antidepressants is that 2-4 weeks of continuous treatment is required to elicit therapeutic effects, prolonging the period of depression, disability and suicide risk. Therefore, the development of fast-onset antidepressants is crucial. Preclinical identification of fast-onset antidepressants requires animal models that can accurately predict the delay to therapeutic onset. Although several well-validated assay models exist that predict antidepressant potential, few thoroughly tested animal models exist that can detect therapeutic onset...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28319198/methamphetamine-induces-shati-nat8l-expression-in-the-mouse-nucleus-accumbens-via-creb-and-dopamine-d1-receptor-dependent-mechanism
#17
Kyosuke Uno, Toh Miyazaki, Kengo Sodeyama, Yoshiaki Miyamoto, Atsumi Nitta
Shati/Nat8L significantly increased in the nucleus accumbens (NAc) of mice after repeated methamphetamine (METH) treatment. We reported that Shati/Nat8L overexpression in mouse NAc attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference. We recently found that Shati/Nat8L overexpression in NAc regulates the dopaminergic neuronal system via the activation of group II mGluRs by elevated N-acetylaspartylglutamate following N-acetylaspartate increase due to the overexpression...
2017: PloS One
https://www.readbyqxmd.com/read/28285415/naag-peptidase-inhibitors-act-via-mglur3-animal-models-of-memory-alzheimer-s-and-ethanol-intoxication
#18
Rafal T Olszewski, Karolina J Janczura, Tomasz Bzdega, Elise K Der, Faustino Venzor, Brennen O'Rourke, Timothy J Hark, Kirsten E Craddock, Shankar Balasubramanian, Charbel Moussa, Joseph H Neale
Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1...
March 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28275711/the-kinase-function-of-msk1-regulates-bdnf-signaling-to-creb-and-basal-synaptic-transmission-but-is-not-required-for-hippocampal-long-term-potentiation-or-spatial-memory
#19
Stephanie Daumas, Christopher J Hunter, Rajen B Mistry, Lorenzo Morè, Lucia Privitera, Daniel D Cooper, Kathleen M Reyskens, Harry T Flynn, Richard G M Morris, J Simon C Arthur, Bruno G Frenguelli
The later stages of long-term potentiation (LTP) in vitro and spatial memory in vivo are believed to depend upon gene transcription. Accordingly, considerable attempts have been made to identify both the mechanisms by which transcription is regulated and indeed the gene products themselves. Previous studies have shown that deletion of one regulator of transcription, the mitogen- and stress-activated kinase 1 (MSK1), causes an impairment of spatial memory. Given the ability of MSK1 to regulate gene expression via the phosphorylation of cAMP response element binding protein (CREB) at serine 133 (S133), MSK1 is a plausible candidate as a prime regulator of transcription underpinning synaptic plasticity and learning and memory...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28273557/curcumin-inhibiting-th17-cell-differentiation-by-regulating-the-metabotropic-glutamate-receptor-4-expression-on-dendritic-cells
#20
Guangming Zhao, Ying Liu, Xiaying Yi, Yupeng Wang, Song Qiao, Zhen Li, Jing Ni, Zhiqi Song
Th17 cells have been categorized as a new lineage of CD4+ T cells, and played a crucial role in the pathogenesis of numerous autoimmune disorders. Type 4 metabotropic glutamate receptor (mGluR4), a member of group III mGluRs, recently has been found to be expressed in many types of immune cells and mediate adaptive immunity. Curcumin has been shown to exhibit potent anti-inflammatory, antimutagenic and anticarcinogenic properties. For the past few years, it has gradually been regarded as an pluripotent immunomodulatory agent that can regulate the activation of immune cells...
March 4, 2017: International Immunopharmacology
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