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Agonists of mGluRs II/III attenuate the staurosporine-induced toxicity in human neuroblastoma SH-SY5Y cells

100%

Jantas D. , Laskiewicz M. , Pilc A. , Lason W.

nr 1

Agonists of metabotropic glutamate receptors group II and III (mGluRs II/III) show neuroprotective effects in in vitro and in vivo models of excitotoxicity. However, their influence on neuronal apoptosis remains unknown. In this study the effect of agonists of mGluRs II/III on staurosporine (St)-evoked LDH release was estimated in undifferentiated (UN-) and retinoic acid (RA)-differentiated human neuroblastoma SH-SY5Y cells. It has been found that LY354740 (0.01-100 microM) and ACTP-I (0.01-100 microM), a nonspecific agonists of mGluRs group II and III, respectively when given alone had no effect on cell proliferation and cell viability. However, both of these compounds partially decreased the St-induced cell death in UN- and RA-SHSY5Y. The selective agonist of mGluR7, AMN082 in low concentrations (0.001-1 microM) had no effect on cell proliferation/viability and tended to attenuate the Stinduced toxicity only in UN-SHSY5Y. On the other hand, AMN082 in higher concentrations (>10 microM) had the cell damaging effect in both UN- and RA- SHSY5Y cells. This study indicates that agonists of mGluRs II/III have potential to attenuate cell death evoked by staurosporine - a well recognized inducer of apoptosis. Acknowledgment: The study was supported by grant No NN405611638 from the Ministry of Science and Higher Education, Warsaw, Poland.

Involvement of protein kinase a in the mechanism of antidepressant action

100%

Palucha A. , Branski P. , Kroczka B. , Pilc A.

Acta Neurobiologiae Experimentalis

1999

tom 59

nr 3

Endurance training increases plasma brain-derived neurotrophic factor concentration in young healthy men

75%

Zoladz J. A. , Pilc A. , Majerczak J. , Grandys M. , Zapart-Bukowska J. , Duda K.

2008

tom 59

nr 7

NS398 (COX-2 INHIBITOR) potentiates the antidepressant-like effects of MTEP (MGLUR5 ANTAGONIST): Involvement of 5-HT system

75%

Stachowicz K. , Sowa-Kucma M. , Lenda T. , Misztak P. , Panczyszyn-Trzewik P. , Nowak G. , Pilc A.

nr Suppl.1

INTRODUCTION: Compounds acting via metabotropic glutamate (mGlu) receptors, exhibit antidepressant activity. Moreover, development of depressive-like behavior in mice is accompanied by elevated level of prostaglandins. In our earlier study, augmentation of antidepressant-like effects of MTEP by NS398 was presented. AIM(S): The aim of this research was to verify the involvement of serotoninergic(5-HT) system in this interaction. METHOD(S): C57Bl/6J male mice were co-treated with MTEP(1 mg/kg; i.p.) and NS398 (3 mg/kg; i.p.) for 7 or 14 days. 24 h after last injection, hippocampus(Hp) and prefrontal cortex(pFC) were collected. The tissue 5-HT and 5-HIAA levels were measured using P680 HPLC system(Dionex, Sunnyvale, CA, USA). Data presented as the mean ±SEM, using one-way ANOVA(n=7–9, Newman-Keuls test), p<0.05 was considered as statistically significant. RESULTS: 14 days co-administration of MTEP with NS398 resulted in statistical significant increase (by 48%) of 5-HT level in pFC [p<0.0001], comparing to the 5-HT level observed after 7 days of administration. Similar picture (increase by 47%) was observed in pFC in 5‑HIAA level [p<0.01]. Quite different picture of changes was observed in Hp, as 5‑HT level was significantly decreased (by 36%) between 7 and 14 days of co-administration of both MTEP with NS398 [p<0.01]. 5-HT:5-HIAA turnover in pFC and Hp, comparing 7 vs. 14 days of co-treatment MTEP with NS398, showed no significant changes[ns]. CONCLUSIONS: Our findings revealed that, chronic co‑treatment MTEP with NS398 affects 5‑HT level in examined brain structures of mice. Observed effect was without changes in 5-HT:5-HIAA turnover, between 7 and 14 days of administration, in pFC and HP of C57Bl/6J mice. This kind of modulation of 5-HT system maybe interesting in the field of psychopharmacology. Further studies are necessary to determine the precise mechanism of interaction of mentioned pathways. FINANCIAL SUPPORT: Study supported by grant UMO-2014/13/D/NZ7/00292.