BAYGEN Institute

Szeged, Hungary

BAYGEN Institute

Szeged, Hungary

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Szegedi V.,BAYGEN Institute | Juhasz G.,University of Szeged | Zhang X.,Karolinska Institutet | Barkoczi B.,BAYGEN Institute | And 6 more authors.
Neurochemistry International | Year: 2011

Impairments of cellular plasticity appear to underlie the pathophysiology of major depression. Recently, elevated levels of phosphorylated AMPA receptor were implicated in the antidepressant effect of various drugs. Here, we investigated the effects of an antidepressant, Tianeptine, on synaptic function and GluA1 phosphorylation using murine hippocampal slices and in vivo single-unit recordings. Tianeptine, but not imipramine, increased AMPA receptor-mediated neuronal responses both in vitro and in vivo, in a staurosporine-sensitive manner. Paired-pulse ratio was unaltered by Tianeptine, suggesting a postsynaptic site of action. Tianeptine, 10 μM, enhanced the GluA1-dependent initial phase of LTP, whereas 100 μM impaired the latter phases, indicating a critical role of GluA1 subunit phosphorylation in the excitation. Tianeptine rapidly increased the phosphorylation level of Ser 831-GluA1 and Ser 845-GluA1. Using H-89 and KN-93, we show that the activation of both PKA and CaMKII is critical in the effect of Tianeptine on AMPA responses. Moreover, the phosphorylation states of Ser 217/221-MEK and Thr 183/Tyr 185-p42MAPK were increased by Tianeptine and specific kinase blockers of the MAPK pathways (PD 98095, SB 203580 and SP600125) prevented the effects of Tianeptine. Overall these data suggest that Tianeptine potentiates several signaling cascades associated with synaptic plasticity and provide further evidence that a major mechanism of action for Tianeptine is to act as an enhancer of glutamate neurotransmission via AMPA receptors. © 2011 Elsevier B.V. All rights reserved.


Maroti G.,BayGen Institute | Rakhely G.,Hungarian Academy of Sciences | Rakhely G.,University of Szeged | Maroti J.,Hungarian Academy of Sciences | And 5 more authors.
International Journal of Hydrogen Energy | Year: 2010

The purple photosynthetic bacterium, Thiocapsa roseopersicina harbours at least three functional [NiFe] hydrogenases. Two of them are attached to the periplasmic membrane (HynSL, HupSL), while the third one is apparently localized in the cytoplasm (HoxEFUYH). Two hypC-type genes, coding for putative small maturation proteins, were found and their roles were studied by activity measurements performed with hypC mutants. Protein-protein interaction experiments confirmed that each HypC-type protein participates in the maturation of at least two [NiFe] hydrogenase large subunits via direct interaction. Endopeptidases perform the last step of the complex [NiFe] hydrogenase maturation process. A separate endopeptidase (HynD, HupD, HoxW) cleaves off the C-terminus of each large subunit and they are strictly specific for their corresponding hydrogenases. The results demonstrate a sophisticated assembly of these functionally active redox metalloenzymes through specific and selective protein-protein interactions and imply some diversity in the hydrogenase assembly machinery among the various microbes. © 2009 Professor T. Nejat Veziroglu.


Maroti J.,Hungarian Academy of Sciences | Farkas A.,BayGen Institute | Nagy I.K.,BayGen Institute | Maroti G.,BayGen Institute | And 5 more authors.
Applied and Environmental Microbiology | Year: 2010

Three functional NiFe hydrogenases were previously characterized in Thiocapsa roseopersicina BBS: two of them are attached to the periplasmic membrane (HynSL and HupSL), and one is localized in the cytoplasm (HoxEFUYH). The ongoing genome sequencing project revealed the presence of genes coding for another soluble Hox-type hydrogenase enzyme (hox2FUYH). Hox2 is a heterotetrameric enzyme; no Indication for an additional subunit was found. Detailed comparative in vivo and in vitro activity and expression analyses of HoxEFUYH (Hox1) and the newly discovered Hox2 enzyme were performed. Functional differences between the two soluble NiFe hydrogenases were disclosed. Hoxl seems to be connected to both sulfur metabolism and dark/photofermentative processes. The bidirectional Hox2 hydrogenase was shown to be metabolically active under specific conditions: it can evolve hydrogen in the presence of glucose at low sodium thiosulfate concentration. However, under nitrogen-fixing conditions, it can oxidize H2 but less than the other hydrogenases in the cell. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Uhasz G.J.,University of Szeged | Barkoczi B.,BAYGEN Institute | Vass G.,University of Szeged | Datki Z.,BAYGEN Institute | And 6 more authors.
Journal of Alzheimer's Disease | Year: 2010

The aggregated form of amyloid-β (Aβ)1-42 has been shown to increase N-methyl-D-aspartic acid (NMDA) evoked neuronal activity in vivo. Here we further characterized this phenomenon by investigating the role of integrin activation and downstream Src kinase activity using in vivo electrophysiology and in vitro intracellular Ca2+ measurements. Pretreatment of differentiated SH-SY5Y cells with fibrillar Aβ 1-42 markedly enhanced the intracellular calcium increases caused by NMDA receptor (NMDA-R) stimulation. Function blocking antibody against β1 integrin depressed the facilitatory effects of Aβ1-42. Similarly, Aβ1-42 facilitated NMDA-R driven firing of hippocampal neurons in vivo, and this effect was reduced by neutralizing antibody against β1 integrins. The positive action of Aβ 1-42 on NMDA-R dependent responses was also depressed by an inhibitor known to block Src kinase. These results support the hypothesis that aggregated Aβ1-42 is recognized by the β1 subunit containing integrins and may induce a Src kinase dependent NMDA receptor phosphorylation. © 2010 - IOS Press and the authors. All rights reserved.


PubMed | BAYGEN Institute
Type: Journal Article | Journal: Journal of neural transmission (Vienna, Austria : 1996) | Year: 2010

Antagonising the NMDA (N-methyl-D: -aspartate) receptor complex is a widely hypothesised therapeutic approach in several neurodegenerative conditions, such as Alzheimers disease. Memantine, a moderate affinity uncompetitive NMDA receptor antagonist, has been in clinical use for several years and numerous experimental data support its NMDA receptor blocking effects. It has recently been reported in transfected HEK293T cells that physiological concentrations of Mg(2+) may impart partial NMDA receptor subtype selectivity and weaken the overall inhibitory actions of memantine in NMDA receptor-mediated cellular events. In the present study, we set out to investigate the effect of intravenously applied memantine on iontophoresed NMDA-evoked firing of hippocampal CA1 neurons using in vivo conditions. Cumulative doses of memantine in the rat (4, 8 and 16 mg/kg i.v.) caused the firing rate to decrease in a dose-dependent manner to 77 7, 58 8 and 34 12% of control, respectively, while saline application had no significant effect. We show that therapeutic doses of memantine are able to antagonize NMDA receptor-mediated activity in the principal cells of the hippocampus in vivo, i.e. in the presence of physiological concentrations of Mg(2+).

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