TY - JOUR AU - Berkecz, Róbert AU - Körmöczi, Tímea AU - Tömösi, Ferenc AU - Szegedi, Viktor AU - Horváth, János AU - Nóra, Kovács AU - Janáky, Tamás TI - Plasma phospholipid profiling of a mouse model of anxiety disorder by hydrophilic interaction liquid chromatography coupled to high-resolution mass spectrometry JF - BIOMEDICAL CHROMATOGRAPHY J2 - BIOMED CHROMATOGR VL - 32 PY - 2018 IS - 6 PG - 9 SN - 0269-3879 DO - 10.1002/bmc.4202 UR - https://m2.mtmt.hu/api/publication/3344638 ID - 3344638 N1 - cited By 0 LA - English DB - MTMT ER - TY - JOUR AU - Berkecz, Róbert AU - Tömösi, Ferenc AU - Körmöczi, Tímea AU - Szegedi, Viktor AU - Horváth, János AU - Janáky, Tamás TI - Comprehensive phospholipid and sphingomyelin profiling of different brain regions in mouse model of anxiety disorder using online two-dimensional (HILIC/RP)-LC/MS method JF - JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS J2 - J PHARMACEUT BIOMED ANAL VL - 149 PY - 2018 SP - 308 EP - 317 PG - 10 SN - 0731-7085 DO - 10.1016/j.jpba.2017.10.043 UR - https://m2.mtmt.hu/api/publication/3292067 ID - 3292067 N1 - Megjegyzés-27030149 N1 Funding details: EFOP-3.6.1-16-2016-00008, MTA, Magyar Tudományos Akadémia N1 Funding text: Róbert Berkecz thanks for the financial support of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences. This research was supported by the EU-funded Hungarian grant EFOP-3.6.1-16-2016-00008. Appendix A AB - A novel online system including two-dimensional liquid chromatography coupled to high-resolution mass spectrometry (2D-LC/MS) was developed and applied for comprehensive phospholipid (PL) and sphingomyelin (SM) profiling of dorsal hippocampus (DHPC), ventral (VHPC) and prefrontal cortex (PFC) brain regions in a mouse model of anxiety disorder. In the first dimension, lipid classes were distinguished by hydrophilic interaction liquid chromatography (HILIC), while the second dimensional separation of individual PL and SM species was achieved by reversed-phase (RP) chromatography. For the enrichment of lipid species in diluted HILIC effluent, two RP trapping columns were used separately. The developed fully-automated 2D method allowed the quantitative analysis of over 150 endogenous PL and SM species in mouse brain regions within 40min. The developed method was applied in a pilot study, which aimed to find alteration of PL and SM composition in a mouse model of anxiety disorder. In the case of 37 PL and SM species, significant differences were observed between high anxiety-related behavior (AX) and low anxiety-related behavior (nAX) mice. In mice having elevated anxiety, the most typical trend was the downregulation of PL species, in particular, in VHPC. LA - English DB - MTMT ER - TY - JOUR AU - Horváth, Gyöngyi AU - Petrovszki, Zita AU - Kékesi, Gabriella AU - Tuboly, Gábor AU - Bodosi, Balázs AU - Horváth, János AU - Gombkötő, Péter AU - Benedek, György AU - Nagy, Attila TI - Electrophysiological alterations in a complex rat model of schizophrenia JF - BEHAVIOURAL BRAIN RESEARCH J2 - BEHAV BRAIN RES VL - 307 PY - 2016 SP - 65 EP - 72 PG - 8 SN - 0166-4328 DO - 10.1016/j.bbr.2016.03.051 UR - https://m2.mtmt.hu/api/publication/3069496 ID - 3069496 AB - BACKGROUND: Psychiatric disorders are frequently accompanied by changes in brain electrical oscillations and abnormal auditory event related potentials. The goal of this study was to characterize these parameters of a new rat substrain showing several alterations related to schizophrenia. METHODS: Male rats of the new substrain, developed by selective breeding after combined subchronic ketamine treatment and postweaning social isolation, and naive Wistar ones group-housed without any interventions were involved in the present study. At the age of 3 months, animals were implanted with cortical electroencephalography electrodes. Auditory evoked potentials during paired-click stimuli and power of oscillation in different frequency bands were determined with and without acute ketamine (20mg/kg) treatment. RESULTS: Regarding the auditory evoked potentials, the latency of P2 was delayed and the amplitude of N1 peak was lower in the new substrain. The new substrain showed increased power of oscillations in the theta, alpha and beta bands, while decreased power was detected in delta and gamma2 bands (52-70Hz) compared with control animals. Acute ketamine treatment increased the gamma1 band (30-48Hz) power in both groups, while it elicited significant changes only in the new substrain in the total power and in alpha, beta and gamma2 bands. CONCLUSIONS: The validation of the translational utility of this new rat substrain by electrophysiological investigations revealed that these rats show abnormalities that may model a part of the neurophysiological deficits observed in schizophrenia. LA - English DB - MTMT ER - TY - JOUR AU - Horváth, János AU - Barkóczi, Balázs Zoltán AU - Muller, G AU - Szegedi, Viktor TI - Anxious and Nonanxious Mice Show Similar Hippocampal Sensory Evoked Oscillations under Urethane Anesthesia: Difference in the Effect of Buspirone JF - NEURAL PLASTICITY J2 - NEURAL PLAST VL - 2015 PY - 2015 IS - 2015 PG - 9 SN - 2090-5904 DO - 10.1155/2015/186323 UR - https://m2.mtmt.hu/api/publication/2891030 ID - 2891030 AB - Hippocampal oscillations recorded under urethane anesthesia are proposed to be modulated by anxiolytics. All classes of clinically effective anxiolytics were reported to decrease the frequency of urethane theta; however, recent findings raise concerns about the direct correlation of anxiolysis and the frequency of hippocampal theta. Here, we took advantage of our two inbred mouse strains displaying extremes of anxiety (anxious (AX) and nonanxious (nAX)) to compare the properties of hippocampal activity and to test the effect of an anxiolytic drugs. No difference was observed in the peak frequency or in the peak power between AX and nAX strains. Buspirone (Bus) applied in 2.5mg/kg decreased anxiety of AX but did not have any effect on nAX as was tested by elevated plus maze and open field. Interestingly, Bus treatment increased hippocampal oscillatory frequency in the AX but left it unaltered in nAX mice. Saline injection did not have any effect on the oscillation. Paired-pulse facilitation was enhanced by Bus in the nAX, but not in the AX strain. Collectively, these results do not support the hypothesis that hippocampal activity under urethane may serve as a marker for potential anxiolytic drugs. Moreover, we could not confirm the decrease of frequency after anxiolytic treatment. LA - English DB - MTMT ER - TY - CONF AU - Furdan, Szabina AU - Borbély, Emőke AU - Horváth, János AU - Penke, Botond AU - Fülöp, Lívia TI - Effects of chronically injected neuroprotective compound on spatial memory and hippocampal dendritic spine density in APP/PS1 transgenic mice T2 - IBRO Workshop 2014 PY - 2014 SP - 95 EP - 95 PG - 1 UR - https://m2.mtmt.hu/api/publication/3086948 ID - 3086948 LA - English DB - MTMT ER - TY - JOUR AU - Borbély, Emőke AU - Horváth, János AU - Furdan, Szabina AU - Bozsó, Zsolt AU - Penke, Botond AU - Fülöp, Lívia TI - Simultaneous changes of spatial memory and spine density after intrahippocampal administration of fibrillar abeta1-42 to the rat brain JF - BIOMED RESEARCH INTERNATIONAL J2 - BIOMED RES INT VL - 2014 PY - 2014 PG - 9 SN - 2314-6133 DO - 10.1155/2014/345305 UR - https://m2.mtmt.hu/api/publication/2755872 ID - 2755872 AB - Several animal models of Alzheimer's disease have been used in laboratory experiments. Intrahippocampal injection of fibrillar amyloid-beta (fAbeta) peptide represents one of the most frequently used models, mimicking Abeta deposits in the brain. In our experiment synthetic fAbeta1-42 peptide was administered to rat hippocampus. The effect of the Abeta peptide on spatial memory and dendritic spine density was studied. The fAbeta1-42-treated rats showed decreased spatial learning ability measured in Morris water maze (MWM). Simultaneously, fAbeta1-42 caused a significant reduction of the dendritic spine density in the rat hippocampus CA1 region. The decrease of learning ability and the loss of spine density were in good correlation. Our results prove that both methods (MWM and dendritic spine density measurement) are suitable for studying Abeta-triggered neurodegeneration processes. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Erzsébet Melinda AU - Szegedi, Viktor AU - Varga, Edina AU - Juhász, Gábor AU - Horváth, János AU - Borbély, Emőke AU - Csibrány, Balázs AU - Alföldi, Róbert AU - Lénárt, Nikolett AU - Penke, Botond AU - Sántha, Miklós TI - Overexpression of Hsp27 ameliorates symptoms of Alzheimer's disease in APP/PS1 mice JF - CELL STRESS & CHAPERONES J2 - CELL STRESS CHAPERON VL - 18 PY - 2013 IS - 6 SP - 759 EP - 771 PG - 13 SN - 1355-8145 DO - 10.1007/s12192-013-0428-9 UR - https://m2.mtmt.hu/api/publication/2365063 ID - 2365063 AB - Hsp27 belongs to the small heat shock protein family, which are ATP-independent chaperones. The most important function of Hsp27 is based on its ability to bind non-native proteins and inhibit the aggregation of incorrectly folded proteins maintaining them in a refolding-competent state. Additionally, it has anti-apoptotic and antioxidant activities. To study the effect of Hsp27 on memory and synaptic functions, amyloid-β (Aβ) accumulation, and neurodegeneration, we generated transgenic mice overexpressing human Hsp27 protein and crossed with APPswe/PS1dE9 mouse strain, a mouse model of Alzheimer's disease (AD). Using different behavioral tests, we found that spatial learning was impaired in AD model mice and was rescued by Hsp27 overexpression. Electrophysiological recordings have revealed that excitability of neurons was significantly increased, and long-term potentiation (LTP) was impaired in AD model mice, whereas they were normalized in Hsp27 overexpressing AD model mice. Using anti-amyloid antibody, we counted significantly less amyloid plaques in the brain of APPswe/PS1dE9/Hsp27 animals compared to AD model mice. These results suggest that overexpression of Hsp27 protein might ameliorate certain symptoms of AD. © 2013 Cell Stress Society International. LA - English DB - MTMT ER - TY - JOUR AU - Horváth, János AU - Szögi, Titanilla AU - Müller, G AU - Szegedi, Viktor TI - The anxiolytic buspirone shifts coping strategy in novel environmental context of mice with different anxious phenotype JF - BEHAVIOURAL BRAIN RESEARCH J2 - BEHAV BRAIN RES VL - 250 PY - 2013 SP - 32 EP - 38 PG - 7 SN - 0166-4328 DO - 10.1016/j.bbr.2013.04.014 UR - https://m2.mtmt.hu/api/publication/2365062 ID - 2365062 N1 - N1 : Chemicals/CASbuspirone, 33386-08-2, 36505-84-7 AB - Patients suffering from anxiety disorders show increased fear when encounter a novel environment. Rodents, placed in new environmental context may respond either with increased novelty seeking (active), or enhanced anxiety (passive coping style), which may depend on the trait anxiety of the animal. Here, the connection between the initial level of anxiety and the behavioral responses in a novel environment was investigated. Two inbred mouse strains having either high- or low-anxiety related behavior (AX and nAX) were exposed to elevated plus maze (EPM), a standard test for assessing anxiety level, for 8 consecutive days. The initial anxiety level was modulated by chronic treatment with buspirone (bus) treatment, a clinically effective anxiolytic, using 2.5. mg/kg and 5.0. mg/kg doses. Both strains showed a gradual decrease of open-arm exploration, which was not prevented by bus treatment. Another cohort of animals was exposed to EPM for 2 days, and then we changed to blue light illumination and used a different cleaning substance with citrus odor (context change, CC). It was found that upon CC AX mice exhibited increased, while nAX mice showed decreased anxiety. Bus in 2.5. mg/kg changed the coping strategy from passive to active exploration after CC in the AX mice; however, the same treatment rendered nAX mice passive upon CC. Bus in 5.0. mg/kg failed to alter the overall coping style in the novel environment of both strains. These results suggest that these mouse lines use different coping strategy in novel context, which can be changed with bus treatment. © 2013 Elsevier B.V. LA - English DB - MTMT ER - TY - JOUR AU - Lénárt, Nikolett AU - Szegedi, Viktor AU - Juhász, Gábor AU - Kasztner, Anikó AU - Horváth, János AU - Bereczki, Erika AU - Tóth, Erzsébet Melinda AU - Penke, Botond AU - Sántha, Miklós TI - Increased Tau Phosphorylation and Impaired Presynaptic Function in Hypertriglyceridemic ApoB-100 Transgenic Mice JF - PLOS ONE J2 - PLOS ONE VL - 7 PY - 2012 IS - 9 PG - 12 SN - 1932-6203 DO - 10.1371/journal.pone.0046007 UR - https://m2.mtmt.hu/api/publication/2101104 ID - 2101104 AB - Aims: ApoB-100 is the major protein component of cholesterol- and triglyceride-rich LDL and VLDL lipoproteins in the serum. Previously, we generated and partially described transgenic mice overexpressing the human ApoB-100 protein. Here, we further characterize this transgenic strain in order to reveal a possible link between hypeprlipidemia and neurodegeneration. Methods and Results: We analyzed the serum and cerebral lipid profiles, tau phosphorylation patterns, amyloid plaque-formation, neuronal apoptosis and synaptic plasticity of young (3 month old), adult (6 month old) and aging (10-11 month old) transgenic mice. We show that ApoB-100 transgenic animals present i) elevated serum and cerebral levels of triglycerides and ApoB-100, ii) increased cerebral tau phosphorylation at phosphosites Ser 199, Ser 199/202, Ser 396 and Ser 404. Furthermore, we demonstrate, that tau hyperphosphorylation is accompanied by impaired presynaptic function, long-term potentiation and widespread hippocampal neuronal apoptosis. Conclusions: The results presented here indicate that elevated ApoB-100 level and the consequent chronic hypertriglyceridemia may lead to impaired neuronal function and neurodegeneration, possibly via hyperphosphorylation of tau protein. On account of their specific phenotype, ApoB-100 transgenic mice may be considered a versatile model of hyperlipidemia-induced age-related neurodegeneration. © 2012 Lénárt et al. LA - English DB - MTMT ER - TY - JOUR AU - Bodóné Sipos, Eszter AU - Kurunczi, Anita AU - Andras, F AU - Penke, Zs AU - Fülöp, Lívia AU - Kasza, Ágnes AU - Horváth, János AU - Horvát, Sándor AU - Veszelka, Szilvia AU - Balogh, Gábor AU - Kürti, Levente AU - Erős, István AU - Révész, Piroska AU - Párducz, Árpád AU - Penke, Botond AU - Deli, Mária Anna TI - Intranasal Delivery of Human beta-Amyloid Peptide in Rats: Effective Brain Targeting JF - CELLULAR AND MOLECULAR NEUROBIOLOGY J2 - CELL MOL NEUROBIOL VL - 30 PY - 2010 IS - 3 SP - 405 EP - 413 PG - 9 SN - 0272-4340 DO - 10.1007/s10571-009-9463-6 UR - https://m2.mtmt.hu/api/publication/1361261 ID - 1361261 AB - (1) Intranasal administration is a non-invasive and effective way for the delivery of drugs to brain that circumvents the blood-brain barrier. The aims of the study were to test a nasal delivery system for human beta-amyloid (A beta) peptides, to measure the delivery of the peptides to brain regions, and to test their biological activity in rats. (2) A beta(1-42), in the form of a mixture of oligomers, protofibrils, and fibrils was dissolved in a nasal formulation containing hydrophobic, hydrophylic, and mucoadhesive components. The peptide solution was administered intranasally to rats as a single dose or in repeated doses. (3) Nasally injected A beta labeled with the blue fluorescent dye amino-methyl coumarinyl acetic acid (AMCA) could be detected by fluorescent microscopy in the olfactory bulb and frontal cortex. The concentration of the peptide was quantified by fluorescent spectroscopy, and a significant amount of AMCA-A beta peptide could be detected in the olfactory bulb. Unlabeled A beta also reached the olfactory bulb and frontal cortex of rats as evidenced by intense immunostaining. (4) In behavioral experiments, nasal A beta treatment did not affect anxiety levels (open-field test) and short-term memory (Y-maze test), but significantly impaired long-term spatial memory in the Morris water maze. The treatments did not result in A beta immunization. (5) The tested intranasal delivery system could successfully target a bioactive peptide into the central nervous system and provides a basis for developing a non-invasive and cost effective, new model to study amyloid-induced dysfunctions in the brain. LA - English DB - MTMT ER -