TY - JOUR AU - Nyitrai, Gabriella AU - Kiss, Béla AU - Farkas, Bence AU - Balázs, O. AU - Diószegi, P. AU - Lendvai, Balázs AU - Czurkó, András TI - Cariprazine modulates sleep architecture in rats JF - JOURNAL OF PSYCHOPHARMACOLOGY J2 - J PSYCHOPHARMACOL VL - 35 PY - 2021 IS - 3 SP - 303 EP - 310 PG - 8 SN - 0269-8811 DO - 10.1177/0269881120981378 UR - https://m2.mtmt.hu/api/publication/31825377 ID - 31825377 LA - English DB - MTMT ER - TY - JOUR AU - Tukacs, Vanda AU - Mittli, Dániel Árpád AU - Györffy, Balázs AU - Hunyadi-Gulyás Éva, Csilla AU - Hlatky, Dávid AU - Tóth, Vilmos AU - Ravasz, Lilla AU - Medzihradszky F., Katalin AU - Nyitrai, Gabriella AU - Czurkó, András AU - Juhász, Gábor Dénes AU - Kardos, József AU - Kékesi, Adrienna Katalin TI - Chronic stepwise cerebral hypoperfusion differentially induces synaptic proteome changes in the frontal cortex, occipital cortex, and hippocampus in rats JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 10 PY - 2020 IS - 1 PG - 12 SN - 2045-2322 DO - 10.1038/s41598-020-72868-w UR - https://m2.mtmt.hu/api/publication/31613493 ID - 31613493 N1 - ELTE NAP Neuroimmunology Research Group, Department of Biochemistry, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary Laboratory of Proteomics, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary Preclinical Imaging Center, Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary Laboratory of Proteomics Research, Biological Research Centre, Szeged, Hungary Department of Biochemistry, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary Department of Physiology and Neurobiology, Institute of Biology, ELTE Eötvös Loránd University, Budapest, Hungary Cited By :7 Export Date: 10 October 2023 Correspondence Address: Kékesi, K.A.; Laboratory of Proteomics, Hungary; email: kakekesi@ttk.elte.hu LA - English DB - MTMT ER - TY - JOUR AU - Spisák, Tamás AU - Román, Viktor AU - Papp, Edit AU - Kedves, Rita AU - Sághy, Katalin AU - Csölle, Cecília AU - Varga, Anita AU - Gajári, Dávid AU - Nyitrai, Gabriella AU - Spisák, Zsófia AU - Kincses, Zsigmond Tamás AU - Lévay, György István AU - Lendvai, Balázs AU - Czurkó, András TI - Purkinje cell number-correlated cerebrocerebellar circuit anomaly in the valproate model of autism JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 9 PY - 2019 IS - 1 PG - 15 SN - 2045-2322 DO - 10.1038/s41598-019-45667-1 UR - https://m2.mtmt.hu/api/publication/30816395 ID - 30816395 N1 - Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary Department of Neurology, University Hospital Essen, Essen, Germany Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Department of Neurology, University of Szeged, Szeged, Hungary Cited By :13 Export Date: 1 September 2023 Correspondence Address: Czurkó, A.; Pharmacology and Drug Safety Research, Hungary; email: czurkoa@richter.hu Chemicals/CAS: valproic acid, 1069-66-5, 99-66-1; Calbindins; Valproic Acid Funding details: ERNYO-13-1-2013-0003, KMOP-1.1.5-08-2009-0001 Funding details: Gedeon Richter Funding text 1: The authors are thankful to Prof. Dagmar Timmann-Braun for her most valuable insights regarding the interpretation of the cerebrocerebellar aspects of our results. The authors are also grateful for the technical assistance of Anita Bérces, Tiborné Gyarmati, Pálma Diószegi and Katalin Tóthné Fekete. This work was supported by Gedeon Richter Plc. and the Hungarian National Research, Development and Innovation Office (KMOP-1.1.5-08-2009-0001, ERNYO-13-1-2013-0003). AB - While cerebellar alterations may play a crucial role in the development of core autism spectrum disorder (ASD) symptoms, their pathophysiology on the function of cerebrocerebellar circuit loops is largely unknown. We combined multimodal MRI (9.4 T) brain assessment of the prenatal rat valproate (VPA) model and correlated immunohistological analysis of the cerebellar Purkinje cell number to address this question. We hypothesized that a suitable functional MRI (fMRI) paradigm might show some altered activity related to disrupted cerebrocerebellar information processing. Two doses of maternal VPA (400 and 600 mg/kg, s.c.) were used. The higher VPA dose induced 3% smaller whole brain volume, the lower dose induced 2% smaller whole brain volume and additionally a focal gray matter density decrease in the cerebellum and brainstem. Increased cortical BOLD responses to whisker stimulation were detected in both VPA groups, but it was more pronounced and extended to cerebellar regions in the 400 mg/kg VPA group. Immunohistological analysis revealed a decreased number of Purkinje cells in both VPA groups. In a detailed analysis, we revealed that the Purkinje cell number interacts with the cerebral BOLD response distinctively in the two VPA groups that highlights atypical function of the cerebrocerebellar circuit loops with potential translational value as an ASD biomarker. LA - English DB - MTMT ER - TY - JOUR AU - Nyitrai, Gabriella AU - Spisák, Tamás AU - Spisák, Z AU - Gajári, D AU - Diószegi, P AU - Kincses, Zsigmond Tamás AU - Czurkó, András TI - Stepwise occlusion of the carotid arteries of the rat. MRI assessment of the effect of donepezil and hypoperfusion-induced brain atrophy and white matter microstructural changes TS - MRI assessment of the effect of donepezil and hypoperfusion-induced brain atrophy and white matter microstructural changes JF - PLOS ONE J2 - PLOS ONE VL - 13 PY - 2018 IS - 5 PG - 25 SN - 1932-6203 DO - 10.1371/journal.pone.0198265 UR - https://m2.mtmt.hu/api/publication/3400976 ID - 3400976 N1 - Preclinical Imaging Center, Pharmacology and Drug Safety Research, Gedeon Richter Plc, Budapest, Hungary Department of Neurology, Albert Szent-Györgyi Clinical Center, University of Szeged, Szeged, Hungary Cited By :10 Export Date: 4 September 2023 CODEN: POLNC Correspondence Address: Nyitrai, G.; Preclinical Imaging Center, Hungary; email: nyitraige@richter.hu Chemicals/CAS: donepezil, 120011-70-3, 120014-06-4, 142057-77-0; gadobutrol, 138071-82-6, 770691-21-9; oxygen, 7782-44-7; donepezil; Indans; Oxygen; Piperidines Tradenames: gadovist, Bayer, Germany Manufacturers: Bayer, GermanyVarian, United States Funding details: European Commission, EC, EFOP-3.6.1-16-2016-00008 Funding details: Gedeon Richter Funding details: National Brain Research Centre, NBRC, KTIA_13_NAP-A-II/20 Funding details: Secretaría de Estado de Investigación, Desarrollo e Innovación, SEIDI Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH, KMOP-1.1.5-08-2009-0001, KTIA_NAP_13-1-2013-0001 Funding details: National Key Research and Development Program of China, NKRDPC, KTIA 13 NAP-A-II/3 Funding text 1: The study was supported by Gedeon Richter Plc., the Hungarian National Research, Development and Innovation Office (KMOP-1.1.5-08-2009-0001, KTIA_NAP_13-1-2013-0001), the National Brain Research Program (Grant No. KTIA_13_NAP-A-II/20. and KTIA 13 NAP-A-II/3) and an EU-funded Hungarian grant EFOP-3.6.1-16-2016-00008. The funders provided support in the form of salaries for authors [G.Ny, A.C, T.S, Zs.S, D.G, P.D], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the’author contributions’ section. AB - Bilateral common carotid artery occlusion (BCCAo) in the rat is a widely used animal model of vascular dementia and a valuable tool for preclinical pharmacological drug testing, although the varying degrees of acute focal ischemic lesions it induces could interfere with its translational value. Recently, a modification to the BCCAo model, the stepwise occlusion of the two carotid arteries, has been introduced. To acquire objective translatable measures, we used longitudinal multimodal magnetic resonance imaging (MRI) to assess the effects of semi-chronic (8 days) donepezil treatment in this model, with half of the Wistar rats receiving the treatment one week after the stepwise BCCAo. With an ultrahigh field MRI, we measured high-resolution anatomy, diffusion tensor imaging, cerebral blood flow measurements and functional MRI in response to whisker stimulation, to evaluate both the structural and functional effects of the donepezil treatment and stepwise BCCAo up to 5 weeks post-occlusion. While no large ischemic lesions were detected, atrophy in the striatum and in the neocortex, along with widespread white matter microstructural changes, were found. Donepezil ameliorated the transient drop in the somatosensory BOLD response in distant cortical areas, as detected 2 weeks after the occlusion but the drug had no effect on the long term structural changes. Our results demonstrate a measurable functional MRI effect of the donepezil treatment and the importance of diffusion MRI and voxel based morphometry (VBM) analysis in the translational evaluation of the rat BCCAo model. LA - English DB - MTMT ER - TY - JOUR AU - Keszthelyi, Tamás AU - Holló, Gábor AU - Nyitrai, Gabriella AU - Kardos, Julianna AU - Héja, László TI - Bilayer Charge Reversal and Modification of Lipid Organization by Dendrimers as Observed by Sum-Frequency Vibrational Spectroscopy JF - LANGMUIR J2 - LANGMUIR VL - 31 PY - 2015 IS - 28 SP - 7815 EP - 7825 PG - 11 SN - 0743-7463 DO - 10.1021/acs.langmuir.5b00734 UR - https://m2.mtmt.hu/api/publication/2932290 ID - 2932290 N1 - Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Budapest, H-1117, Hungary Cited By :9 Export Date: 7 April 2021 CODEN: LANGD Correspondence Address: Keszthelyi, T.; Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok körútja 2, Hungary AB - Polyamidoamine (PAMAM) dendrimers are hyper-branched, nanosized polymers with promising biomedical applications as nanocarriers in targeted drug delivery and gene therapy. For the development of safe dendrimer-based biomedical applications it is necessary to gain an understanding of the detailed mechanism of the interactions of both cationic and anionic dendrimers with cell membranes. To characterize dendrimer membrane interactions we applied solid-supported lipid bilayers as biomembrane models and utilized infrared visible sum-frequency vibrational spectroscopy to independently probe the interactions of cationic G5-NH2 and anionic G4.5-COONa dendrimers with the two leaflets of the lipid bilayers. Interaction with both dendrimers led to changes in the interfacial water structure and charge density as evidenced by the changes in the OH band intensities in the sum-frequency spectra of the bilayers. Interaction with the G5-NH2 dendrimer also led to a unique inversion of the sign of the OH-stretch amplitudes, in addition to a decrease in their absolute values. We suggest that the positively charged amino groups on the G5-NH2 dendrimer surface bind to the negatively charged bilayer, while uncompensated positive charges not involved in the binding cause a reversal of the electric field and thus an opposite orientation of the interfacial water molecules. More subtle but nonetheless significant changes were seen in the relative magnitudes of the CH amplitudes. The methyl antisymmetric to symmetric stretch amplitude ratios are altered, implying changes in the tilt angles of the phospholipid alkyl chains. The conformational order of the phospholipid alkyl chains of both leaflets is also influenced by the G5-NH2 dendrimer while G4.5-COONa has no effect on the alkyl chain conformation. LA - English DB - MTMT ER - TY - JOUR AU - Kékesi, Orsolya Sára AU - Nyitrai, Gabriella AU - Szabó, Pál Tamás AU - Fiáth, Richárd AU - Ulbert, István AU - Kardos, Julianna AU - Héja, László TI - GLIAL GABA TRANSPORTERS DOWNREGULATE ENHANCED NEURONAL ACTIVITY JF - GLIA J2 - GLIA VL - 61 PY - 2013 IS - 1 SP - S122 EP - S123 PG - 2 SN - 0894-1491 UR - https://m2.mtmt.hu/api/publication/2540335 ID - 2540335 N1 - 11th European Meeting on Glial Cell Function in Health and Disease JUL 03-06, 2013. Berlin, GERMANY SU 1 LA - English DB - MTMT ER - TY - JOUR AU - Nyitrai, Gabriella AU - Keszthelyi, Tamás AU - Bóta, Attila AU - Simon, Ágnes AU - Tőke, Orsolya AU - Horváth, Gergő AU - Pál, Ildikó AU - Kardos, Julianna AU - Héja, László TI - Sodium selective ion channel formation in living cell membranes by polyamidoamine dendrimer JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES J2 - BBA-BIOMEMBRANES VL - 1828 PY - 2013 IS - 8 SP - 1873 EP - 1880 PG - 8 SN - 0005-2736 DO - 10.1016/j.bbamem.2013.04.004 UR - https://m2.mtmt.hu/api/publication/2305528 ID - 2305528 N1 - Megjegyzés-23246857 N1 : Chemicals/CAScalcium ion, 14127-61-8; dipalmitoylphosphatidylcholine, 2644-64-6; silicon dioxide, 10279-57-9, 14464-46-1, 14808-60-7, 15468-32-3, 60676-86-0, 7631-86-9; sodium ion, 17341-25-2 LA - English DB - MTMT ER - TY - JOUR AU - Nyitrai, Gabriella AU - Héja, László AU - Jablonkai, István AU - Pál, Ildikó AU - Benéné Visy, Júlia AU - Kardos, Julianna TI - Polyamidoamine dendrimer impairs mitochondrial oxidation in brain tissue JF - JOURNAL OF NANOBIOTECHNOLOGY J2 - J NANOBIOTECHNOL VL - 11 PY - 2013 PG - 9 SN - 1477-3155 DO - 10.1186/1477-3155-11-9 UR - https://m2.mtmt.hu/api/publication/2305501 ID - 2305501 AB - Background: The potential nanocarrier polyamidoamine (PAMAM) generation 5 (G5-NH2) dendrimer has been shown to evoke lasting neuronal depolarization and cell death in a concentration-dependent manner. In this study we explored the early progression of G5-NH2 action in brain tissue on neuronal and astroglial cells.Results: In order to describe early mechanisms of G5-NH2 dendrimer action in brain tissue we assessed G5-NH2 trafficking, free intracellular Ca2+ and mitochondrial membrane potential (ΨMITO) changes in the rat hippocampal slice by microfluorimetry. With the help of fluorescent dye conjugated G5-NH2, we observed predominant appearance of the dendrimer in the plasma membrane of pyramidal neurons and glial cells within 30 min. Under this condition, G5-NH2 evoked robust intracellular Ca2+ enhancements and ΨMITO depolarization both in pyramidal neurons and astroglial cells. Intracellular Ca2+ enhancements clearly preceded ΨMITO depolarization in astroglial cells. Comparing activation dynamics, neurons and glia showed prevalence of lasting and transient ΨMITO depolarization, respectively. Transient as opposed to lasting ΨMITO changes to short-term G5-NH2 application suggested better survival of astroglia, as observed in the CA3 stratum radiatum area. We also showed that direct effect of G5-NH2 on astroglial ΨMITO was significantly enhanced by neuron-astroglia interaction, subsequent to G5-NH2 evoked neuronal activation.Conclusion: These findings indicate that the interaction of the PAMAM dendrimer with the plasma membrane leads to robust activation of neurons and astroglial cells, leading to mitochondrial depolarization. Distinguishable dynamics of mitochondrial depolarization in neurons and astroglia suggest that the enhanced mitochondrial depolarization followed by impaired oxidative metabolism of neurons may be the primary basis of neurotoxicity. © 2013 Nyitrai et al.; licensee BioMed Central Ltd. LA - English DB - MTMT ER - TY - JOUR AU - Pál, Ildikó AU - Nyitrai, Gabriella AU - Kardos, Julianna AU - Héja, László TI - Neuronal and Astroglial Correlates Underlying Spatiotemporal Intrinsic Optical Signal in the Rat Hippocampal Slice JF - PLOS ONE J2 - PLOS ONE VL - 8 PY - 2013 IS - 3 SN - 1932-6203 DO - 10.1371/journal.pone.0057694 UR - https://m2.mtmt.hu/api/publication/2222611 ID - 2222611 N1 - Published: March 01, 2013 Funding Agency and Grant Number: [ERA-Chemistry OTKA 102166]; [TECH-09-AI-2009-0117 NKFP NANOSEN9] Funding text: This work was supported by grants ERA-Chemistry OTKA 102166 (http://www.otka.hu/) and TECH-09-AI-2009-0117 NKFP NANOSEN9 (http://www.nih.gov.hu/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Cited By :22 Export Date: 6 April 2021 Correspondence Address: Pál, I.; Department of Functional Pharmacology, , Budapest, Hungary; email: pal.ildiko@ttk.mta.hu LA - English DB - MTMT ER - TY - JOUR AU - Nyitrai, Gabriella AU - Kékesi, Orsolya Sára AU - Pál, Ildikó AU - Keglevich, Péter AU - Csíki, Zsuzsanna AU - Fügedi, Péter AU - Simon, Ágnes AU - Fitos, Ilona AU - Németh, Krisztina AU - Benéné Visy, Júlia AU - Tárkányi, Gábor AU - Kardos, Julianna TI - Assessing toxicity of polyamidoamine dendrimers by neuronal signaling functions JF - NANOTOXICOLOGY J2 - NANOTOXICOLOGY VL - 6 PY - 2012 IS - 6 SP - 576 EP - 586 PG - 11 SN - 1743-5390 DO - 10.3109/17435390.2011.591511 UR - https://m2.mtmt.hu/api/publication/2060849 ID - 2060849 N1 - Early Online: pp. 1-13. (2011) Funding Agency and Grant Number: Nanotransport [CRC-HAS_2009]; NANOSEN9 [TECH-09-A1-2009-0117]; [GVOP-3.2.1.-2004-04-0210/3.0] Funding text: We thank Nanotransport (CRC-HAS_2009), NANOSEN9 (TECH-09-A1-2009-0117) and GVOP-3.2.1.-2004-04-0210/3.0 projects for financial support. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. LA - English DB - MTMT ER -