TY - JOUR AU - Barabási, Beáta AU - Barna, Lilla AU - Santa Maria, Anaraquel AU - Harazin, András AU - Molnár, Réka AU - Kincses, András AU - Vigh, Judit Piroska AU - Dukay, Brigitta AU - Sántha, Miklós AU - Tóth, Erzsébet Melinda AU - Walter, Fruzsina AU - Deli, Mária Anna AU - Hoyk, Zsófia TI - Role of interleukin-6 and interleukin-10 in morphological and functional changes of the blood–brain barrier in hypertriglyceridemia JF - FLUIDS AND BARRIERS OF THE CNS J2 - FLUIDS BARRIERS CNS VL - 20 PY - 2023 IS - 1 PG - 20 SN - 2045-8118 DO - 10.1186/s12987-023-00418-3 UR - https://m2.mtmt.hu/api/publication/33688118 ID - 33688118 N1 - Funding Agency and Grant Number: ELKH Biological Research Center - National Research, Development, and Innovation Office of Hungary [GINOP-2.3.2-15-2016-00060]; European Training Network [H2020-MSCA-ITN-2015, 675619] Funding text: Open access funding provided by ELKH Biological Research Center. This work was funded by the National Research, Development, and Innovation Office of Hungary, Grant Number GINOP-2.3.2-15-2016-00060. ARSM was supported by the European Training Network H2020-MSCA-ITN-2015 [Grant Number 675619]. LA - English DB - MTMT ER - TY - JOUR AU - Szögi, Titanilla AU - Borbély, Emőke AU - Schuster, Ildikó AU - Bozsó, Zsolt AU - Sántha, Miklós AU - Tóth, Erzsébet Melinda AU - Penke, Botond AU - Fülöp, Lívia TI - Examination of Longitudinal Alterations in Alzheimer’s Disease-Related Neurogenesis in an APP/PS1 Transgenic Mouse Model, and the Effects of P33, a Putative Neuroprotective Agent Thereon JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 18 PG - 17 SN - 1661-6596 DO - 10.3390/ijms231810364 UR - https://m2.mtmt.hu/api/publication/33111245 ID - 33111245 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Office [GINOP-2.3.2-15-2016-00060]; Hungarian Brain Research Program I and II [KTIA_13_NAP-A-III/7, 2017-1.2.1-NKP-2017-00002]; Ministry of Human Capacities, Hungary [20391-3/2018/FEKUSTRAT]; Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund [TKP2021-EGA-32] Funding text: This project was supported by the National Research, Development and Innovation Office (GINOP-2.3.2-15-2016-00060) and by the Hungarian Brain Research Program I and II (Grant No. KTIA_13_NAP-A-III/7, and 2017-1.2.1-NKP-2017-00002). Support by the Ministry of Human Capacities, Hungary (grant 20391-3/2018/FEKUSTRAT) and the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund (TKP2021-EGA-32) is acknowledged. AB - Neurogenesis plays a crucial role in cognitive processes. During aging and in Alzheimer’s disease (AD), altered neurogenesis and neuroinflammation are evident both in C57BL/6J, APPSwe/PS1dE9 (Tg) mice and humans. AD pathology may slow down upon drug treatment, for example, in a previous study of our group P33, a putative neuroprotective agent was found to exert advantageous effects on the elevated levels of APP, Aβ, and neuroinflammation. In the present study, we aimed to examine longitudinal alterations in neurogenesis, neuroinflammation and AD pathology in a transgenic (Tg) mouse model, and assessed the putative beneficial effects of long-term P33 treatment on AD-specific neurological alterations. Hippocampal cell proliferation and differentiation were significantly reduced between 8 and 12 months of age. Regarding neuroinflammation, significantly elevated astrogliosis and microglial activation were observed in 6- to 7-month-old Tg animals. The amounts of the molecules involved in the amyloidogenic pathway were altered from 4 months of age in Tg animals. P33-treatment led to significantly increased neurogenesis in 9-month-old animals. Our data support the hypothesis that altered neurogenesis may be a consequence of AD pathology. Based on our findings in the transgenic animal model, early pharmacological treatment before the manifestation of AD symptoms might ameliorate neurological decline. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Erzsébet Melinda AU - Sárközy, Márta AU - Szűcs, Gergő AU - Dukay, Brigitta AU - Hajdu, Petra AU - Zvara, Ágnes AU - Puskás, László AU - Szebeni, Gábor AU - Ruppert, Zsófia AU - Csonka, Csaba AU - Kovács, Ferenc AU - Kriston, András AU - Horváth, Péter AU - Kővári, Bence AU - Cserni, Gábor AU - Csont, Tamás Bálint AU - Sántha, Miklós TI - Exercise training worsens cardiac performance in males but does not change ejection fraction and improves hypertrophy in females in a mouse model of metabolic syndrome JF - BIOLOGY OF SEX DIFFERENCES J2 - BIOL SEX DIFFER VL - 13 PY - 2022 IS - 1 PG - 20 SN - 2042-6410 DO - 10.1186/s13293-022-00414-6 UR - https://m2.mtmt.hu/api/publication/32637299 ID - 32637299 N1 - Laboratory of Animal Genetics and Molecular Neurobiology, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, Szeged, 6726, Hungary MEDICS Research Group, Department of Biochemistry, University of Szeged Albert Szent-Györgyi Medical School, Dóm tér 9, Szeged, 6720, Hungary Interdisciplinary Center of Excellence, University of Szeged, Dugonics tér 13, Szeged, 6720, Hungary Laboratory of Functional Genomics, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, Szeged, 6726, Hungary Doctoral School in Biology, University of Szeged, Szeged, Hungary Synthetic and Systems Biology Unit, Institute of Biochemistry, Biological Research Centre, Eötvös Loránd Research Network, Temesvári krt. 62, Szeged, 6726, Hungary Single-Cell Technologies Ltd, Temesvári krt. 62, Szeged, 6726, Hungary Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, 00014, Finland Department of Pathology, Albert Szent-Györgyi Medical School, University of Szeged, Állomás utca 1, Szeged, LA - English DB - MTMT ER - TY - JOUR AU - Varga-Medveczky, Zsófia AU - Stelczerné Kovács, Noémi AU - Tóth, Erzsébet Melinda AU - Sántha, Miklós AU - Horváth, Ildikó AU - Bors, Luca Anna AU - Fónagy, Katalin AU - Imre, Timea AU - Szabó, Pál Tamás AU - Máthé, Domokos AU - Erdő, Franciska TI - Age-Related Inflammatory Balance Shift, Nasal Barrier Function, and Cerebro-Morphological Status in Healthy and Diseased Rodents JF - FRONTIERS IN NEUROSCIENCE J2 - FRONT NEUROSCI-SWITZ VL - 15 PY - 2021 PG - 15 SN - 1662-4548 DO - 10.3389/fnins.2021.700729 UR - https://m2.mtmt.hu/api/publication/32113140 ID - 32113140 N1 - Faculty of Information Technology and Bionics, Pázmány Péter Catholic University, Budapest, Hungary Department of Biophysics and Radiation Biology, Faculty of Medicine, Semmelweis University, Budapest, Hungary Institute of Biochemistry, ELKH Biological Research Centre, Szeged, Hungary Heart and Vascular Centre, Faculty of Medicine, Semmelweis University, Budapest, Hungary Research Centre for Natural Sciences, Centre for Structural Study, Budapest, Hungary Hungarian Center of Excellence for Molecular Medicine (HCEMM), Budapest, Hungary Cited By :2 Export Date: 28 February 2024 Correspondence Address: Erdő, F.; Faculty of Information Technology and Bionics, Hungary; email: erdo.franciska@itk.ppke.hu LA - English DB - MTMT ER - TY - JOUR AU - Sompol, Pradoldej AU - Gollihue, Jenna L. AU - Kraner, Susan D. AU - Artiushin, Irina A. AU - Cloyd, Ryan A. AU - Chishti, Emad A. AU - Koren, Shon A. AU - Nation, Grant K. AU - Abisambra, Jose F. AU - Huzian, Orsolya AU - Nagy, Lajos I. AU - Sántha, Miklós AU - Hackler, Laszlo Jr. AU - Puskás, László AU - Norris, Christopher M. TI - Q134R: Small chemical compound with NFAT inhibitory properties improves behavioral performance and synapse function in mouse models of amyloid pathology JF - AGING CELL J2 - AGING CELL VL - 20 PY - 2021 IS - 7 SN - 1474-9718 DO - 10.1111/acel.13416 UR - https://m2.mtmt.hu/api/publication/32078131 ID - 32078131 N1 - Export Date: 16 June 2022 CODEN: ACGEC AB - Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. However, small chemical inhibitors of NFATs have only rarely been described. Here, we investigate a newly developed neuroprotective hydroxyquinoline derivative (Q134R) that suppresses NFAT signaling, without inhibiting CN activity. Q134R partially inhibited NFAT activity in primary rat astrocytes, but did not prevent CN-mediated dephosphorylation of a non-NFAT target, either in vivo, or in vitro. Acute (<= 1 week) oral delivery of Q134R to APP/PS1 (12 months old) or wild-type mice (3-4 months old) infused with oligomeric A beta peptides led to improved Y maze performance. Chronic (>= 3 months) oral delivery of Q134R appeared to be safe, and, in fact, promoted survival in wild-type (WT) mice when given for many months beyond middle age. Finally, chronic delivery of Q134R to APP/PS1 mice during the early stages of amyloid pathology (i.e., between 6 and 9 months) tended to reduce signs of glial reactivity, prevented the upregulation of astrocytic NFAT4, and ameliorated deficits in synaptic strength and plasticity, without noticeably altering parenchymal A beta plaque pathology. The results suggest that Q134R is a promising drug for treating AD and aging-related disorders. LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Erzsébet Melinda AU - Dukay, Brigitta AU - Péter, Mária AU - Balogh, Gábor AU - Szűcs, Gergő AU - Zvara, Ágnes AU - Szebeni, Gábor AU - Hajdu, Petra AU - Sárközy, Márta AU - Puskás, László AU - Török, Zsolt AU - Csont, Tamás Bálint AU - Vigh, László AU - Sántha, Miklós TI - Male and Female Animals Respond Differently to High-Fat Diet and Regular Exercise Training in a Mouse Model of Hyperlipidemia JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 8 PG - 22 SN - 1661-6596 DO - 10.3390/ijms22084198 UR - https://m2.mtmt.hu/api/publication/31970009 ID - 31970009 N1 - Institute of Biochemistry, ELKH Biological Research Centre, Szeged, H-6726, Hungary Doctoral School in Biology, University of Szeged, Szeged, H-6726, Hungary MEDICS Research Group, Department of Biochemistry, Interdisciplinary Center of Excellence, University of Szeged, Szeged, H-6720, Hungary Laboratory of Functional Genomics, ELKH Biological Research Centre, Szeged, H-6726, Hungary Export Date: 14 May 2021 Correspondence Address: Tóth, M.E.; Institute of Biochemistry, Hungary; email: toth.erzsebetmelinda@brc.hu Institute of Biochemistry, ELKH Biological Research Centre, Szeged, H-6726, Hungary Doctoral School in Biology, University of Szeged, Szeged, H-6726, Hungary MEDICS Research Group, Department of Biochemistry, Interdisciplinary Center of Excellence, University of Szeged, Szeged, H-6720, Hungary Laboratory of Functional Genomics, ELKH Biological Research Centre, Szeged, H-6726, Hungary Export Date: 22 May 2021 Correspondence Address: Tóth, M.E.; Institute of Biochemistry, Hungary; email: toth.erzsebetmelinda@brc.hu AB - Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We aimed to analyze the morphological, gene expression, and lipidomic patterns in the liver and adipose tissues in response to regular exercise. Healthy (wild type on a normal diet) and hyperlipidemic, high-fat diet-fed (HFD-fed) apolipoprotein B-100 (APOB-100)-overexpressing mice were trained by treadmill running for 7 months. The serum concentrations of triglyceride and tumor necrosis factor alpha (TNF alpha), as well as the level of lipid accumulation in the liver, were significantly higher in HFD-fed APOB-100 males compared to females. However, regular exercise almost completely abolished lipid accumulation in the liver of hyperlipidemic animals. The expression level of the thermogenesis marker, uncoupling protein-1 (Ucp1), was significantly higher in the subcutaneous white adipose tissue of healthy females, as well as in the brown adipose tissue of HFD-fed APOB-100 females, compared to males. Lipidomic analyses revealed that hyperlipidemia essentially remodeled the lipidome of brown adipose tissue, affecting both the membrane and storage lipid fractions, which was partially restored by exercise in both sexes. Our results revealed more severe metabolic disturbances in HFD-fed APOB-100 males compared to females. However, exercise efficiently reduced the body weight, serum triglyceride levels, expression of pro-inflammatory factors, and hepatic lipid accumulation in our model. LA - English DB - MTMT ER - TY - JOUR AU - Dukay, Brigitta AU - Walter, Fruzsina AU - Vigh, Judit Piroska AU - Barabási, Beáta AU - Hajdu, Petra AU - Balassa, Tamás AU - Migh, Ede AU - Kincses, András AU - Hoyk, Zsófia AU - Szögi, Titanilla AU - Borbély, Emőke AU - Csoboz, Bálint AU - Horváth, Péter AU - Fülöp, Lívia AU - Penke, Botond AU - Vigh, László AU - Deli, Mária Anna AU - Sántha, Miklós AU - Tóth, Erzsébet Melinda TI - Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury JF - JOURNAL OF NEUROINFLAMMATION J2 - J NEUROINFLAMM VL - 18 PY - 2021 IS - 1 PG - 24 SN - 1742-2094 DO - 10.1186/s12974-020-02070-2 UR - https://m2.mtmt.hu/api/publication/31807147 ID - 31807147 N1 - Miklós Sántha and Melinda E. Tóth are shared last authors. LA - English DB - MTMT ER - TY - JOUR AU - Sántha, Miklós TI - Biologia futura: animal testing in drug development-the past, the present and the future JF - BIOLOGIA FUTURA J2 - BIOL FUTURA VL - 71 PY - 2020 IS - 4 SP - 443 EP - 452 PG - 10 SN - 2676-8615 DO - 10.1007/s42977-020-00050-4 UR - https://m2.mtmt.hu/api/publication/31670054 ID - 31670054 AB - Animal experiments have served to improve our knowledge on diseases and treatment approaches since ancient times. Today, animal experiments are widely used in medical, biomedical and veterinary research, and are essential means of drug development and preclinical testing, including toxicology and safety studies. Recently, great efforts have been made to replace animal experiments with in vitro organoid culture methods and in silico predictions, in agreement with the 3R strategy to "reduce, refine and replace" animals in experimental testing, as outlined by the European Commission. Here we present a mini-review on the development of animal testing, as well as on alternative in vitro and in silico methods, that may at least partly replace animal experiments in the near future. LA - English DB - MTMT ER - TY - JOUR AU - Sántha, Miklós AU - Durham, Heather D. AU - Vigh, László AU - Prodromou, Chrisostomos TI - Editorial: The Role of Heat Shock Proteins in Neuroprotection JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 11 PY - 2020 SN - 1663-9812 DO - 10.3389/fphar.2020.01227 UR - https://m2.mtmt.hu/api/publication/31599677 ID - 31599677 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Erzsébet Melinda AU - Dukay, Brigitta AU - Hoyk, Zsófia AU - Sántha, Miklós TI - Cerebrovascular Changes and Neurodegeneration Related to Hyperlipidemia. Characteristics of the Human ApoB-100 Transgenic Mice. TS - Characteristics of the Human ApoB-100 Transgenic Mice. JF - CURRENT PHARMACEUTICAL DESIGN J2 - CURR PHARM DESIGN VL - 26 PY - 2020 IS - 13 SP - 1486 EP - 1494 PG - 9 SN - 1381-6128 DO - 10.2174/1381612826666200218101818 UR - https://m2.mtmt.hu/api/publication/31195696 ID - 31195696 N1 - Cited By :6 Export Date: 15 September 2022 CODEN: CPDEF AB - Serum lipid levels are closely related to the structure and function of blood vessels. Chronic hyperlipidemia may lead to damage in both the cardio- and the cerebrovascular systems. Vascular dysfunctions, including impairments of the blood-brain barrier, are known to be associated with neurodegenerative diseases. A growing number of evidence suggests that cardiovascular risk factors, such as hyperlipidemia, may increase the likelihood of developing dementia. Due to differences in lipoprotein metabolism, wild-type mice are protected against diet-induced hypercholesterolemia, and their serum lipid profile is different from that observed in humans. Therefore, several transgenic mouse models have been established to study the role of different apolipoproteins and their receptors in lipid metabolism, as well as the complications related to pathological lipoprotein levels. This mini-review will focus on a transgenic mouse model overexpressing an apolipoprotein, the human ApoB-100. We will discuss literature data and current advancements on the understanding of ApoB-100 induced cardio- and cerebrovascular lesions in order to demonstrate the involvement of this type of apolipoprotein in a wide range of pathologies, and a link between hyperlipidemia and neurodegeneration. LA - English DB - MTMT ER -