TY - JOUR AU - Siket, Máté AU - Novak, K. AU - Eigner, György AU - Kovács, László Ákos TI - MEAL ESTIMATION ACCURACY IN MODEL PREDICTIVE CONTROL-MOVING HORIZON ESTIMATION CONTROL STRATEGY JF - DIABETES TECHNOLOGY AND THERAPEUTICS J2 - DIABETES TECHNOL THE VL - 25 PY - 2023 SP - A112 EP - A112 PG - 1 SN - 1520-9156 UR - https://m2.mtmt.hu/api/publication/34147524 ID - 34147524 LA - English DB - MTMT ER - TY - JOUR AU - Kocsis, G. AU - Garam, Nóra AU - Javorfi, T. AU - Svebis, M. AU - Toth, B. AU - Ferenci, Tamás AU - Eigner, György AU - Barkai, L. AU - Kovács, László Ákos TI - THE IMPACT OF MINIMED (TM) 780G INSULIN PUMP SYSTEM - A SINGLE CENTRE PROSPECTIVE STUDY JF - DIABETES TECHNOLOGY AND THERAPEUTICS J2 - DIABETES TECHNOL THE VL - 25 PY - 2023 SP - A70 EP - A70 PG - 1 SN - 1520-9156 UR - https://m2.mtmt.hu/api/publication/34147477 ID - 34147477 LA - English DB - MTMT ER - TY - JOUR AU - Fehér, Máté AU - Márton, Zsombor AU - Szabó, Ákos AU - Kocsa, János AU - Kormos, Viktória AU - Hunyady, Ágnes AU - Kovács, László Ákos AU - Ujvári, Balázs AU - Berta, Gergely AU - Farkas, József AU - Füredi, Nóra AU - Gaszner, Tamás AU - Pytel, Bence AU - Reglődi, Dóra AU - Gaszner, Balázs TI - Downregulation of PACAP and the PAC1 Receptor in the Basal Ganglia, Substantia Nigra and Centrally Projecting Edinger–Westphal Nucleus in the Rotenone model of Parkinson’s Disease JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 14 PG - 24 SN - 1661-6596 DO - 10.3390/ijms241411843 UR - https://m2.mtmt.hu/api/publication/34074467 ID - 34074467 AB - Numerous in vitro and in vivo models of Parkinson’s disease (PD) demonstrate that pituitary adenylate cyclase-activating polypeptide (PACAP) conveys its strong neuroprotective actions mainly via its specific PAC1 receptor (PAC1R) in models of PD. We recently described the decrease in PAC1R protein content in the basal ganglia of macaques in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD that was partially reversed by levodopa therapy. In this work, we tested whether these observations occur also in the rotenone model of PD in the rat. The rotarod test revealed motor skill deterioration upon rotenone administration, which was reversed by benserazide/levodopa (B/L) treatment. The sucrose preference test suggested increased depression level while the open field test showed increased anxiety in rats rendered parkinsonian, regardless of the received B/L therapy. Reduced dopaminergic cell count in the substantia nigra pars compacta (SNpc) diminished the dopaminergic fiber density in the caudate-putamen (CPu) and decreased the peptidergic cell count in the centrally projecting Edinger–Westphal nucleus (EWcp), supporting the efficacy of rotenone treatment. RNAscope in situ hybridization revealed decreased PACAP mRNA (Adcyap1) and PAC1R mRNA (Adcyap1r1) expression in the CPu, globus pallidus, dopaminergic SNpc and peptidergic EWcp of rotenone-treated rats, but no remarkable downregulation occurred in the insular cortex. In the entopeduncular nucleus, only the Adcyap1r1 mRNA was downregulated in parkinsonian animals. B/L therapy attenuated the downregulation of Adcyap1 in the CPu only. Our current results further support the evolutionarily conserved role of the PACAP/PAC1R system in neuroprotection and its recruitment in the development/progression of neurodegenerative states such as PD. LA - English DB - MTMT ER - TY - JOUR AU - Gaszner, Tamás AU - Farkas, József AU - Kun, Dániel AU - Ujvári, Balázs AU - Füredi, Nóra AU - Kovács, László Ákos AU - Hashimoto, Hitoshi AU - Reglődi, Dóra AU - Kormos, Viktória AU - Gaszner, Balázs TI - Epigenetic and Neuronal Activity Markers Suggest the Recruitment of the Prefrontal Cortex and Hippocampus in the Three-Hit Model of Depression in Male PACAP Heterozygous Mice. JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 19 PG - 16 SN - 1661-6596 DO - 10.3390/ijms231911739 UR - https://m2.mtmt.hu/api/publication/33163285 ID - 33163285 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Fund of Hungary [TKP2021-EGA-16, TKP2021-EGA, 2020-4.1.1-TKP2020, TKP2020-IKA08]; Hungarian Scientific Research Fund (NKFIH) [PD100706, FK124188]; Medical Faculty, University of Pecs [KA-2019-12]; National Research, Development, and Innovation Fund [UNKP-225-PTE-1740]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00750/22/5]; Pecs University Medical School [KA-2020-03]; New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund [UNKP-20-4-II-PTE547]; NAP [2017-1.2.1-NKP-2017-00002, MTA-TKI14016] Funding text: This project (TKP2021-EGA-16) was implemented with the support provided by the National Research, Development, and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme and also under the 2020-4.1.1-TKP2020 funding scheme (Project No: TKP2020-IKA08). Our work was also supported by the Hungarian Scientific Research Fund (NKFIH, PD100706, and FK124188) to B.G. and V.K. was sponsored by research grants from the Medical Faculty, University of Pecs (KA-2019-12), National Research, Development, and Innovation Fund (UNKP-225-PTE-1740) and by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00750/22/5). N.F. was supported by research grants from the Pecs University Medical School KA-2020-03, and the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund (UNKP-20-4-II-PTE547). This work was also financed by NAP 2017-1.2.1-NKP-2017-00002 and MTA-TKI14016. AB - Depression and its increasing prevalence challenge patients, the healthcare system, and the economy. We recently created a mouse model based on the three-hit concept of depression. As genetic predisposition (first hit), we applied pituitary adenylate cyclase-activating polypeptide heterozygous mice on CD1 background. Maternal deprivation modeled the epigenetic factor (second hit), and the chronic variable mild stress was the environmental factor (third hit). Fluoxetine treatment was applied to test the predictive validity of our model. We aimed to examine the dynamics of the epigenetic marker acetyl-lysine 9 H3 histone (H3K9ac) and the neuronal activity marker FOSB in the prefrontal cortex (PFC) and hippocampus. Fluoxetine decreased H3K9ac in PFC in non-deprived animals, but a history of maternal deprivation abolished the effect of stress and SSRI treatment on H3K9ac immunoreactivity. In the hippocampus, stress decreased, while SSRI increased H3K9ac immunosignal, unlike in the deprived mice, where the opposite effect was detected. FOSB in stress was stimulated by fluoxetine in the PFC, while it was inhibited in the hippocampus. The FOSB immunoreactivity was almost completely abolished in the hippocampus of the deprived mice. This study showed that FOSB and H3K9ac were modulated in a territory-specific manner by early life adversities and later life stress interacting with the effect of fluoxetine therapy supporting the reliability of our model. LA - English DB - MTMT ER - TY - JOUR AU - Gaszner, Tamás AU - Farkas, József AU - Kun, Dániel AU - Ujvári, Balázs AU - Berta, Gergely AU - Csernus, Valér AU - Füredi, Nóra AU - Kovács, László Ákos AU - Hashimoto, Hitoshi AU - Reglődi, Dóra AU - Kormos, Viktória AU - Gaszner, Balázs TI - Fluoxetine treatment supports predictive validity of the three hit model of depression in male PACAP heterozygous mice and underpins the impact of early life adversity on therapeutic efficacy JF - FRONTIERS IN ENDOCRINOLOGY J2 - FRONT ENDOCRINOL VL - 13 PY - 2022 PG - 23 SN - 1664-2392 DO - 10.3389/fendo.2022.995900 UR - https://m2.mtmt.hu/api/publication/33123834 ID - 33123834 N1 - Funding Agency and Grant Number: National Research, Development and Innovation Fund of Hungary [TKP2021- EGA-16, TKP2021-EGA, 2020-4.1.1-TKP2020, TKP2020IKA-08]; Hungarian Scientific Research Fund (NKFIH) [PD100706, FK124188]; Medical Faculty, University of Pecs [KA-2019-12]; National Research, Development and Innovation Fund [UNKP-22-5-PTE-1740]; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/ 00750/22/5]; Pecs University Medical School [KA-2020-03]; New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund [UNKP-20-4-II-PTE-547]; NAP [2017-1.2.1-NKP-2017-00002, MTA-TKI14016] Funding text: This project (TKP2021- EGA-16) has been implemented with the support provided from the National Research, Development and Innovation Fund of Hungary, financed under the TKP2021-EGA funding scheme and also under the 2020-4.1.1-TKP2020 funding scheme (Project No: TKP2020IKA-08). The work was also supported by the Hungarian Scientific Research Fund (NKFIH, PD100706 and FK124188) to BG. VK was sponsored by the research grant of the Medical Faculty, University of Pe ' cs (KA-2019-12), by National Research, Development and Innovation Fund ( UNKP-22-5-PTE-1740) and by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/ 00750/22/5). NF was supported by the research grant of Pecs University Medical School KA-2020-03, and New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (U ' NKP-20-4-II-PTE-547). This work was also financed by NAP 2017-1.2.1-NKP-2017-00002; MTA-TKI14016. AB - According to the three hit concept of depression, interaction of genetic predisposition altered epigenetic programming and environmental stress factors contribute to the disease. Earlier we demonstrated the construct and face validity of our three hit concept-based mouse model. In the present work, we aimed to examine the predictive validity of our model, the third willnerian criterion. Fluoxetine treatment was applied in chronic variable mild stress (CVMS)-exposed (environmental hit) CD1 mice carrying one mutated allele of pituitary adenylate cyclase-activating polypeptide gene (genetic hit) that were previously exposed to maternal deprivation (epigenetic hit) vs. controls. Fluoxetine reduced the anxiety level in CVMS-exposed mice in marble burying test, and decreased the depression level in tail suspension test if mice were not deprived maternally. History of maternal deprivation caused fundamental functional-morphological changes in response to CVMS and fluoxetine treatment in the corticotropin-releasing hormone-producing cells of the bed nucleus of the stria terminalis and central amygdala, in tyrosine-hydroxylase content of ventral tegmental area, in urocortin 1-expressing cells of the centrally projecting Edinger-Westphal nucleus, and serotonergic cells of the dorsal raphe nucleus. The epigenetic background of alterations was approved by altered acetylation of histone H3. Our findings further support the validity of both the three hit concept and that of our animal model. Reversal of behavioral and functional-morphological anomalies by fluoxetine treatment supports the predictive validity of the model. This study highlights that early life stress does not only interact with the genetic and environmental factors, but has strong influence also on therapeutic efficacy. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, László Ákos AU - Füredi, Nóra AU - Ujvári, Balázs AU - Golgol, Abolfazl AU - Gaszner, Balázs TI - Age-Dependent FOSB/ΔFOSB Response to Acute and Chronic Stress in the Extended Amygdala, Hypothalamic Paraventricular, Habenular, Centrally-Projecting Edinger-Westphal, and Dorsal Raphe Nuclei in Male Rats JF - FRONTIERS IN AGING NEUROSCIENCE J2 - FRONT AGING NEUROSCI VL - 14 PY - 2022 PG - 24 SN - 1663-4365 DO - 10.3389/fnagi.2022.862098 UR - https://m2.mtmt.hu/api/publication/32804334 ID - 32804334 N1 - Funding Agency and Grant Number: New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund [UNKP-20-4-II-PTE-547, GINOP-2.3.2-15-2016-00050, MTA-TKI14016]; PTE-AOK [KA2020-26]; Thematic Excellence Program 2021 Health Sub-program of the Ministry for Innovation and Technology in Hungary; Hungarian Scientific Research Fund (NKFIH) [FK124188, KA2020-03]; Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs Funding text: This work was supported by the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund (UNKP-20-4-II-PTE-563) and the research grant of Pecs University Medical School (No. PTE-AOK KA2020-26). BG was supported by the Thematic Excellence Program 2021 Health Sub-program of the Ministry for Innovation and Technology in Hungary, within the framework of the EGA16 project of Pecs University, and by the Hungarian Scientific Research Fund (NKFIH, FK124188). NF was supported by the research grant of Pecs University Medical School KA2020-03 and the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development, and Innovation Fund (UNKP-20-4-II-PTE-547). GINOP-2.3.2-15-2016-00050 "PEPSYS," MTA-TKI14016; Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs and EFOP-3.6.2-16-2017-00008 "The role of neuroinflammation in neurodegeneration: from molecules to clinics." AB - FOS proteins are early-responding gene products that contribute to the formation of activator protein-1. Several acute and chronic stimuli lead to Fos gene expression, accompanied by an increase of nuclear FOS, which appears to decline with aging. FOSB is another marker to detect acute cellular response, while ΔFOSB mirrors long-lasting changes in neuronal activity upon chronic stress. The notion that the occurrence of stress-related mood disorders shows some age dependence suggests that the brain's stress sensitivity is also a function of age. To study age-dependent stress vulnerability at the immediate-early gene level, we aimed to describe how the course of aging affects the neural responses of FOSB/ΔFOSB in the acute restraint stress (ARS), and chronic variable mild stress (CVMS) in male rats. Fourteen brain areas [central, medial, basolateral (BLA) amygdala; dorsolateral- (BNSTdl), oval- (BNSTov), dorsomedial-, ventral- (BNSTv), and fusiform- (BNSTfu) divisions of the bed nucleus of the stria terminalis; medial and lateral habenula, hypothalamic paraventricular nucleus (PVN), centrally-projecting Edinger-Westphal nucleus, dorsal raphe nucleus, barrel field of somatosensory cortex (S1)] were examined in the course of aging. Eight age groups [1-month-old (M), 1.5 M, 2 M, 3 M, 6 M, 12 M, 18 M, and 24 M] of rats were exposed to a single ARS vs. controls. In addition, rats in six age groups (2, 3, 6, 12, 18, and 24 M) were subjected to CVMS. The FOSB/ΔFOSB immunoreactivity (IR) was a function of age in both controls, ARS- and CVMS-exposed rats. ARS increased the FOSB/ΔFOSB in all nuclei (except in BLA), but only BNSTfu, BNSTv, and PVN reacted throughout the examined lifespan. The CVMS did not increase the FOSB/ΔFOSB in BLA, BNSTov, BNSTdl, and S1. PVN showed a constantly maintained FOSB/ΔFOSB IR during the examined life period. The maximum stress-evoked FOSB/ΔFOSB signal was detected at 2-3 M periods in the ARS- and at 6 M, 18 M in CVMS- model. Corresponding to our previous observations on FOS, the FOSB/ΔFOSB response to stress decreased with age in most of the examined nuclei. Only the PVN exerted a sustained age-independent FOSB/ΔFOSB, which may reflect the long-lasting adaptation response and plasticity of neurons that maintain the hypothalamus-pituitary-adrenal axis response throughout the lifespan. LA - English DB - MTMT ER - TY - JOUR AU - Ujvári, Balázs AU - Pytel, Bence AU - Márton, Zsombor AU - Bognár, Máté AU - Kovács, László Ákos AU - Farkas, József AU - Gaszner, Tamás AU - Berta, Gergely AU - Kecskés, Angéla AU - Kormos, Viktória AU - Farkas, Boglárka AU - Füredi, Nóra AU - Gaszner, Balázs TI - Neurodegeneration in the centrally-projecting Edinger–Westphal nucleus contributes to the non-motor symptoms of Parkinson’s disease in the rat JF - JOURNAL OF NEUROINFLAMMATION J2 - J NEUROINFLAMM VL - 19 PY - 2022 IS - 1 PG - 17 SN - 1742-2094 DO - 10.1186/s12974-022-02399-w UR - https://m2.mtmt.hu/api/publication/32640720 ID - 32640720 AB - The neuropathological background of major depression and anxiety as non-motor symptoms of Parkinson's disease is much less understood than classical motor symptoms. Although, neurodegeneration of the Edinger-Westphal nucleus in human Parkinson's disease is a known phenomenon, its possible significance in mood status has never been elucidated. In this work we aimed at investigating whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger-Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.Systemic chronic rotenone administration as well as targeted leptin-saporin-induced lesions of EWcp/UCN1 neurons were conducted. Rotarod, open field and sucrose preference tests were performed to assess motor performance and mood status. Multiple immunofluorescence combined with RNAscope were used to reveal the functional-morphological changes. Two-sample Student's t test, Spearman's rank correlation analysis and Mann-Whitney U tests were used for statistics.In the rotenone model, besides motor deficit, an anxious and depression-like phenotype was detected. Well-comparable neuron loss, cytoplasmic alpha-synuclein accumulation as well as astro- and microglial activation were observed both in the substantia nigra pars compacta and EWcp. Occasionally, UCN1-immunoreactive neuronal debris was observed in phagocytotic microglia. UCN1 peptide content of viable EWcp cells correlated with dopaminergic substantia nigra cell count. Importantly, other mood status-related dopaminergic (ventral tegmental area), serotonergic (dorsal and median raphe) and noradrenergic (locus ceruleus and A5 area) brainstem centers did not show remarkable morphological changes. Targeted partial selective EWcp/UCN1 neuron ablation induced similar mood status without motor symptoms.Our findings collectively suggest that neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson's disease in the rat. LA - English DB - MTMT ER - TY - BOOK AU - Kovács, Zsófia AU - Kovács, László Ákos AU - Paic, Róbert AU - Solymossy, Mária AU - Kovács, László TI - VÍZ ALATTI SPORTOK VILÁGA I.. AZ USZONYOSÚSZÁS TS - AZ USZONYOSÚSZÁS ET - 1 PB - Wunderlich Production Kft. CY - Budapest PY - 2021 SP - 144 SN - 9786150139937 UR - https://m2.mtmt.hu/api/publication/32804723 ID - 32804723 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Józsa, Gergő AU - Fülöp, Balázs Dániel AU - Kovács, László Ákos AU - Czibere, Bernadett AU - Szegeczki, Vince AU - Kiss, Tamás AU - Hajdú, Tibor AU - Tamás, Andrea AU - Helyes, Zsuzsanna AU - Zákány, Róza AU - Reglődi, Dóra AU - Juhász, Tamás TI - Lack of Pituitary Adenylate Cyclase–Activating Polypeptide (PACAP) Disturbs Callus Formation JF - JOURNAL OF MOLECULAR NEUROSCIENCE J2 - J MOL NEUROSCI VL - 71 PY - 2021 IS - 8 SP - 1543 EP - 1555 PG - 13 SN - 0895-8696 DO - 10.1007/s12031-019-01448-z UR - https://m2.mtmt.hu/api/publication/30935538 ID - 30935538 N1 - * Megosztott szerzőség AB - Pituitary adenylate cyclase–activating polypeptide (PACAP) is a naturally secreted signaling peptide and has important regulatory roles in the differentiation of the central nervous system and its absence results in disorders in femur development. PACAP has an important function in prevention of oxidative stress or mechanical stress in chondrogenesis but little is known about its function in bone regeneration. A new callus formation model was set to investigate its role in bone remodeling. Fracturing was 5 mm distal from the proximal articular surface of the tibia and the depth was 0.5 mm. Reproducibility of callus formation was investigated with CT 3, 7, and 21 days after the operation. Absence of PACAP did not alter the alkaline phosphatase (ALP) activation in PACAP KO healing process. In developing callus, the expression of collagen type I increased in wild-type (WT) and PACAP KO mice decreased to the end of healing process. Expression of the elements of BMP signaling was disturbed in the callus formation of PACAP KO mice, as bone morphogenic protein 4 (BMP4) and 6 showed an early reduction in bone regeneration. However, elevated Smad1 expression was demonstrated in PACAP KO mice. Our results indicate that PACAP KO mice show various signs of disturbed bone healing and suggest PACAP compensatory and fine tuning effects in proper bone regeneration. LA - English DB - MTMT ER - TY - THES AU - Kovács, László Ákos TI - Limbikus és középagyi stressz-asszociált magok korfüggő aktivitásának vizsgálata az akut és krónikus stressz patkánymodelljében PY - 2020 UR - https://m2.mtmt.hu/api/publication/31664192 ID - 31664192 LA - Hungarian DB - MTMT ER -