scholarly journals Proneurogenic Group II mGluR antagonist improves learning and reduces anxiety in Alzheimer Aβ oligomer mouse

2014 ◽  
Vol 19 (11) ◽  
pp. 1235-1242 ◽  
Author(s):  
S H Kim ◽  
J W Steele ◽  
S W Lee ◽  
G D Clemenson ◽  
T A Carter ◽  
...  
Keyword(s):  
Group Ii ◽  
Mglur Antagonist ◽  
Aβ Oligomer

Activation of Group I mGluRs Is Necessary for Induction of Long-Term Depression at Striatal Synapses

2001 ◽  
Vol 86 (5) ◽  
pp. 2405-2412 ◽  
Author(s):  
Ki-Wug Sung ◽  
Sukwoo Choi ◽  
David M. Lovinger
Keyword(s):  
Synaptic Transmission ◽  
Metabotropic Glutamate Receptors ◽  
Brain Slices ◽  
High Frequency Stimulation ◽  
Long Term Depression ◽  
Selective Antagonist ◽  
Group I ◽  
Group Ii ◽  
Mglur Antagonist

Activation of metabotropic glutamate receptors (mGluRs), which are coupled to G proteins, has important roles in certain forms of synaptic plasticity including corticostriatal long-term depression (LTD). In the present study, extracellular field potential and whole cell voltage-clamp recording techniques were used to investigate the effect of mGluR antagonists with different subtype specificity on high-frequency stimulation (HFS)-induced LTD of synaptic transmission in the striatum of brain slices obtained from 15-to 25-day-old rats. Induction of LTD was prevented during exposure to the nonselective mGluR antagonist (RS)-α-methyl-4-carboxyphenylglycine (500 μM). The group I mGluR-selective antagonists ( S)-4-carboxy-phenylglycine (50 μM) and (RS)-1-aminoindan-1,5-dicarboxylic acid (100 μM) prevented induction of LTD when applied before and during HFS. The mGluR1-selective antagonist 7-(Hydroxyimino) cyclopropa[b]chromen-1a-carboxylate ethyl ester (80 μM) also blocked LTD induction. Unexpectedly, the mGluR5-selective antagonist 2-methyl-6-(phenylethyl)-pyridine (10 μM) also prevented LTD induction. The group II mGluR antagonist LY307452 (10 μM) did not block LTD induction at corticostriatal synapses, but LY307452 was able to block transient synaptic depression induced by the group II agonist LY314593. None of the antagonists had any effect on basal synaptic transmission at the concentrations used, and mGluR antagonists did not reverse LTD when applied beginning 20 min after HFS. These results suggest that both group I mGluR subtypes contribute to the induction of LTD at corticostriatal synapses.

Loss of Long-Lasting Potentiation Mediated by Group III mGluRs in Amygdala Neurons in Kindling-Induced Epileptogenesis

1997 ◽  
Vol 78 (6) ◽  
pp. 3475-3478 ◽  
Author(s):  
Volker Neugebauer ◽  
N. Bradley Keele ◽  
Patricia Shinnick-Gallagher
Keyword(s):  
Electrical Stimulation ◽  
Synaptic Transmission ◽  
Learning And Memory ◽  
Metabotropic Glutamate Receptors ◽  
Long Term Potentiation ◽  
Group Iii ◽  
Brain Functions ◽  
Group Ii ◽  
Mglur Antagonist

Neugebauer, Volker, N. Bradley Keele, and Patricia Shinnick-Gallagher. Loss of long-lasting potentiation mediated by group III mGluRs in amygdala neurons in kindling-induced epileptogenesis. J. Neurophysiol. 78: 3475–3478, 1997. Long-lasting modifications of synaptic transmission can be induced in the amygdala by electrical stimulation as done in the long-term potentiation (LTP) model of learning and memory and the kindling model of epilepsy. The present study reports for the first time a long-lasting potentiation (LLP) of synaptic transmission that is induced pharmacologically by the activation of group III metabotropic glutamate receptors (mGluRs) in basolateral amygdala (BLA) neurons. In whole cell voltage-clamp mode, BLA neurons were recorded in brain slices from control rats and rats with amygdala-kindled seizures. The group III mGluR agonist l-2-amino-4-phosphonobutyrate (l-AP4, 10 μM) induced LLP of monosynaptic excitatory postsynaptic currents (EPSCs) evoked by electrical stimulation in the lateral amygdala (maximum 258 ± 50% of predrug control; means ± SE) in control ( n = 7) but not in kindled neurons( n = 6). LLP was measured 15 min after the superfusion of l-AP4, lasted for >45 min, and was not accompanied by postsynaptic membrane changes. l-AP4 induced LLP was prevented by the group III mGluR antagonist (S)-2-methyl-2-amino-4-phosphonobutyrate (MAP4; 100 μM, n = 6) but not the group II mGluR antagonist (2S,3S,4S)-2-methyl-2-carboxycyclopropylglycine (MCCG; 100 μM, n = 3). LLP was not observed after superfusion of the group II mGluR agonist (2S,3S,4S)-2-(carboxycyclopropyl)glycine (l-CCG; 1.0 and 10 μM) in either control ( n = 13) or kindled ( n = 10) neurons. If the underlying mechanisms and the functional significance of pharmacologically induced LLP are similar to those of LTP, the loss of l-AP4 induced LLP in kindled neurons may be a neurobiological correlate of learning and memory deficits in kindled animals and long-term alterations of brain functions in patients with epilepsies.

Prodrugs of 3-(3,4-dichlorobenzyloxy)-2-amino-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039): A potent and orally active group II mGluR antagonist with antidepressant-like potential

2006 ◽  
Vol 14 (12) ◽  
pp. 4193-4207 ◽  
Author(s):  
Akito Yasuhara ◽  
Masato Nakamura ◽  
Kazunari Sakagami ◽  
Toshiharu Shimazaki ◽  
Ryoko Yoshikawa ◽  
...  
Keyword(s):  
Dicarboxylic Acid ◽  
Active Group ◽  
Group Ii ◽  
Orally Active ◽  
Mglur Antagonist

scholarly journals Astrocyte activation of presynaptic metabotropic glutamate receptors modulates hippocampal inhibitory synaptic transmission

2004 ◽  
Vol 1 (4) ◽  
pp. 307-316 ◽  
Author(s):  
QING-SONG LIU ◽  
QIWU XU ◽  
JIAN KANG ◽  
MAIKEN NEDERGAARD
Keyword(s):  
Synaptic Transmission ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Metabotropic Glutamate Receptor ◽  
Hippocampal Slices ◽  
Group Iii ◽  
Inhibitory Synaptic Transmission ◽  
Metabotropic Glutamate ◽  
Group Ii ◽  
Mglur Antagonist

In the CNS, fine processes of astrocytes often wrap around dendrites, axons and synapses, which provides an interface where neurons and astrocytes might interact. We have reported previously that selective Ca2+ elevation in astrocytes, by photolysis of caged Ca2+ by o-nitrophenyl-EGTA (NP-EGTA), causes a kainite receptor-dependent increase in the frequency of spontaneous inhibitory post-synaptic potentials (sIPSCs) in neighboring interneurons in hippocampal slices. However, tetrodotoxin (TTX), which blocks action potentials, reduces the frequency of miniature IPSCs (mIPSCs) in interneurons during Ca2+ uncaging by an unknown presynaptic mechanism. In this study we investigate the mechanism underlying the presynaptic inhibition. We show that Ca2+ uncaging in astrocytes is accompanied by a decrease in the amplitude of evoked IPSCs (eIPSCs) in neighboring interneurons. The decreases in eIPSC amplitude and mIPSC frequency are prevented by CPPG, a group II/III metabotropic glutamate receptor (mGluR) antagonist, but not by the AMPA/kainate and NMDA receptor antagonists CNQX/CPP. Application of either the group II mGluR agonist DCG IV or the group III mGluR agonist L-AP4 decreased the amplitude of eIPSCs by a presynaptic mechanism, and both effects are blocked by CPPG. Thus, activation of mGluRs mediates the effects of Ca2+ uncaging on mIPSCs and eIPSCs. Our results indicate that Ca2+-dependent release of glutamate from astrocytes can activate distinct classes of glutamate receptors and differentially modulate inhibitory synaptic transmission in hippocampal interneurons.

β-NAAG Rescues LTP From Blockade by NAAG in Rat Dentate Gyrus via the Type 3 Metabotropic Glutamate Receptor

2001 ◽  
Vol 85 (3) ◽  
pp. 1097-1106 ◽  
Author(s):  
Paul M. Lea IV ◽  
Barbara Wroblewska ◽  
John M. Sarvey ◽  
Joseph H. Neale
Keyword(s):  
Dentate Gyrus ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Granule Cells ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii ◽  
Type 3 ◽  
Mglur Antagonist ◽  
In Cells

N-Acetylaspartylglutamate (NAAG) is an agonist at the type 3 metabotropic glutamate receptor (mGluR3), which is coupled to a Gi/o protein. When activated, the mGluR3 receptor inhibits adenylyl cyclase and reduces the cAMP-mediated second-messenger cascade. Long-term potentiation (LTP) in the medial perforant path (MPP) of the hippocampal dentate gyrus requires increases in cAMP. The presence of mGluR3 receptors and NAAG in neurons of the dentate gyrus suggests that this peptide transmitter may inhibit LTP in the dentate gyrus. High-frequency stimulation (100 Hz; 2 s) of the MPP resulted in LTP of extracellularly recorded excitatory postsynaptic potentials at the MPP-granule cell synapse of rat hippocampal slices. Perfusion of the slice with NAAG (50 and 200 μM) blocked LTP. Neither 50 nor 200 μM NAAG produced N-methyl-d-aspartate receptor currents in the granule cells of the acute hippocampal slice. The group II mGluR antagonist ethyl glutamate (100 μM) and a structural analogue of NAAG, β-NAAG (100 μM), prevented the blockade of LTP by NAAG. Paired-pulse depression of the excitatory postsynaptic potential at 20- and 80-ms interpulse intervals (IPI) was not affected by NAAG or β-NAAG. β-NAAG did not affect inositol trisphosphate production stimulated by the agonist glutamate in cells expressing the group I mGluR1α or mGluR5. β-NAAG blocked the decrease in forskolin-stimulated cAMP by the group II mGluR agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV) but not the group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid in cerebellar granule cells. In cells transfected with mGluR3, but not mGluR2, β-NAAG blocked forskolin-stimulated cAMP responses to glutamate, NAAG, the nonspecific group I, II agonist trans-ACPD, and the group II agonist DCG-IV. We conclude that β-NAAG is a selective mGluR antagonist capable of differentiating between mGluR2 and mGluR3 subtypes and that the mGluR3 receptor functions to regulate activity-dependent synaptic potentiation in the hippocampus.

scholarly journals Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment

2011 ◽  
Vol 1380 ◽  
pp. 106-119 ◽  
Author(s):  
Catherine H. Choi ◽  
Brian P. Schoenfeld ◽  
Aaron J. Bell ◽  
Paul Hinchey ◽  
Maria Kollaros ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Mouse Model ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Lithium Treatment ◽  
Group Ii ◽  
Mglur Antagonist

Ultrastructural Lesions Produced by Alcohol and Sucrose in the Heart and Liver of C57BL Mice

1970 ◽  
Vol 28 ◽  
pp. 208-209
Author(s):  
K.K. SEKHRI ◽  
C.S. ALEXANDER ◽  
H.T. NAGASAWA
Keyword(s):  
Osmium Tetroxide ◽  
Male Mice ◽  
Alcohol Group ◽  
Group Iii ◽  
Group I ◽  
C57bl Mice ◽  
Group Ii

C57BL male mice (Jackson Lab., Bar Harbor, Maine) weighing about 18 gms were randomly divided into three groups: group I was fed sweetened liquid alcohol diet (modified Schenkl) in which 36% of the calories were derived from alcohol; group II was maintained on a similar diet but alcohol was isocalorically substituted by sucrose; group III was fed regular mouse chow ad lib for five months. Liver and heart tissues were fixed in 2.5% cacodylate buffered glutaraldehyde, post-fixed in 2% osmium tetroxide and embedded in Epon-araldite.

Study of segregation in La1.8Sr0.2CuO4 superconductor by STEM-EDS microanalysis

1987 ◽  
Vol 45 ◽  
pp. 54-55
Author(s):  
T. F. Kelly ◽  
P. J. Lee ◽  
E. E. Hellstrom ◽  
D. C. Larbalestier
Keyword(s):  
Rare Earth ◽  
High Field ◽  
Transport Current ◽  
Total Thickness ◽  
New Class ◽  
Ceramic Superconductors ◽  
Current Densities ◽  
Group Ii ◽  
Eds Microanalysis

Recently there has been much excitement over a new class of high Tc (>30 K) ceramic superconductors of the form A1-xBxCuO4-x, where A is a rare earth and B is from Group II. Unfortunately these materials have only been able to support small transport current densities 1-10 A/cm2. It is very desirable to increase these values by 2 to 3 orders of magnitude for useful high field applications. The reason for these small transport currents is as yet unknown. Evidence has, however, been presented for superconducting clusters on a 50-100 nm scale and on a 1-3 μm scale. We therefore planned a detailed TEM and STEM microanalysis study in order to see whether any evidence for the clusters could be seen.A La1.8Sr0.2Cu04 pellet was cut into 1 mm thick slices from which 3 mm discs were cut. The discs were subsequently mechanically ground to 100 μm total thickness and dimpled to 20 μm thickness at the center.

Heterogeneity and Immunochemical Properties of Anti-β2-glycoprotein I Autoantibodies

1998 ◽  
Vol 80 (09) ◽  
pp. 393-398 ◽  
Author(s):  
V. Regnault ◽  
E. Hachulla ◽  
L. Darnige ◽  
B. Roussel ◽  
J. C. Bensa ◽  
...  
Keyword(s):  
Fluid Phase ◽  
Anticardiolipin Antibodies ◽  
Dual Reactivity ◽  
Group Iii ◽  
Important Group ◽  
Epitope Specificity ◽  
Glycoprotein I ◽  
Group I ◽  
Group Ii ◽  
Sufficient Concentration

SummaryMost anticardiolipin antibodies (ACA) associated with antiphospholipid syndrome (APS) are directed against epitopes expressed on β2-glycoprotein I (β2GPI). Despite a good correlation between standard ACA assays and those using purified human β2GPI as the sole antigen, some sera from APS patients only react in the latter. This is indicative of heterogeneity in anti-β2GPI antibodies. To characterize their reactivity profiles, human and bovine β2GPI were immobilized on γ-irradiated plates (β2GPI-ELISA), plain polystyrene precoated with increasing cardiolipin concentrations (CL/β2GPI-ELISA), and affinity columns. Fluid-phase inhibition experiments were also carried out with both proteins. Of 56 selected sera, restricted recognition of bovine or human β2GPI occurred respectively in 10/29 IgA-positive and 9/22 IgM-positive samples, and most of the latter (8/9) were missed by the standard ACA assay, as expected from a previous study. Based on species specificity and ACA results, IgG-positive samples (53/56) were categorized into three groups: antibodies reactive to bovine β2GPI only (group I) or to bovine and human β2GPI, group II being ACA-negative, and group III being ACA-positive. The most important group, group III (n = 33) was characterized by (i) binding when β2GPI was immobilized on γ-irradiated polystyrene or cardiolipin at sufficient concentration (regardless of β2GPI density, as assessed using 125I-β2GPI); (ii) and low avidity binding to fluid-phase β2GPI (Kd in the range 10–5 M). In contrast, all six group II samples showed (i) ability to bind human and bovine β2GPI immobilized on non-irradiated plates; (ii) concentration-dependent blockade of binding by cardiolipin, suggesting epitope location in the vicinity of the phospholipid binding site on native β2GPI; (iii) and relative avidities approximately 100-fold higher than in group III. Group I patients were heterogeneous with respect to CL/β2GPI-ELISA and ACA results (6/14 scored negative), possibly reflecting antibody differences in terms of avidity and epitope specificity. Affinity fractionation of 23 sera showed the existence, in individual patients, of various combinations of antibody subsets solely reactive to human or bovine β2GPI, together with cross-species reactive subsets present in all samples with dual reactivity namely groups III and II, although the latter antibodies were poorly purified on either column. Therefore, the mode of presentation of β2GPI greatly influences its recognition by anti-β2GPI antibodies with marked inter-individual heterogeneity, in relation to ACA quantitation and, possibly, disease presentation and pathogenesis.

Treatment of venous leg ulcers with sulodexide

Phlebologie ◽  
2003 ◽  
Vol 32 (05) ◽  
pp. 115-120 ◽  
Author(s):  
A. Franek ◽  
H. Koziolek ◽  
M. Kucharzewski
Keyword(s):  
Pharmacological Treatment ◽  
Healing Process ◽  
Leg Ulcers ◽  
Venous Ulceration ◽  
Venous Leg Ulcers ◽  
Group I ◽  
Group Ii

SummaryAim: The study of the influence of sulodexide in the treatment of venous leg ulcers. Patients and method: 44 patients with chronic venous ulceration were randomly divided into two groups. Group I: 21 patients (ulceration area: 12.7-18.9 cm2), Group II: 23 patients (ulceration size: 12.1-20.3 cm2). Both groups were treated by using Unna’s boot. This dressing was changed every seven days until the ulcer had healed. Additionally, the patients in group II received the systemic pharmacological treatment with sulodexide. Results: After 7 weeks of treatment ulcers of seven patients (35%) from group I had healed, and 3 weeks later the ulceration of two more patients had healed completely. After further 7 weeks the ulcers of 12 patients had healed completely. Whereas in group II after 7 weeks of treatment ulceration of 16 (70%, p <0.05) patient had healed completely and after further 3 weeks the ulcers of the remaining 7 patients had healed, too. Conclusion: The use of sulodexide in patients with chronic venous leg ulcers accelerates the healing process.

Sign in / Sign up

Export Citation Format

Share Document