@article{MTMT:34574198, title = {The Lack of TRPA1 Ion Channel Does Not Affect the Chronic Stress-Induced Activation of the Locus Ceruleus}, url = {https://m2.mtmt.hu/api/publication/34574198}, author = {Milicic, Milica and Gaszner, Balázs and Berta, Gergely and Pintér, Erika and Kormos, Viktória}, doi = {10.3390/ijms25031765}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {25}, unique-id = {34574198}, issn = {1661-6596}, abstract = {We have previously proven the involvement of transient receptor potential ankyrin 1 (TRPA1) in stress adaptation. A lack of TRPA1 affects both urocortin 1 (member of the corticotropin-releasing hormone (CRH) family) content of the Edinger-Westphal nucleus. The noradrenergic locus ceruleus (LC) is also an important player in mood control. We aimed at investigating whether the TRPA1 is expressed in the LC, and to test if the response to chronic variable mild stress (CVMS) is affected by a lack of TRPA1. The TRPA1 expression was examined via RNAscope in situ hybridization. We investigated TRPA1 knockout and wildtype mice using the CVMS model of depression. Tyrosine hydroxylase (TH) and FOSB double immunofluorescence were used to test the functional neuromorphological changes in the LC. No TRPA1 expression was detected in the LC. The TH content was not affected by CVMS exposure. The CVMS-induced FOSB immunosignal did not co-localize with the TH neurons. TRPA1 is not expressed in the LC. A lack of functional TRPA1 receptor neither directly nor indirectly affects the TH content of LC neurons under CVMS.}, keywords = {STRESS; DEPRESSION; TRPA1; CVMS}, year = {2024}, eissn = {1422-0067}, orcid-numbers = {Gaszner, Balázs/0000-0003-2830-2732; Pintér, Erika/0000-0001-9898-632X} } @article{MTMT:34478042, title = {Does preheating influence the cytotoxic potential of dental resin composites?}, url = {https://m2.mtmt.hu/api/publication/34478042}, author = {Dunavári, Erika Katalin and Kőházy, A and Vecsernyés, M and Szalma, József and Lovász, Bálint Viktor and Berta, Gergely and Lempel, Edina}, doi = {10.3390/polym16020174}, journal-iso = {POLYMERS-BASEL}, journal = {POLYMERS}, volume = {16}, unique-id = {34478042}, year = {2024}, eissn = {2073-4360}, orcid-numbers = {Szalma, József/0000-0002-6006-8758} } @article{MTMT:34074641, title = {Long-term Effects of the pituitary-adenylate cyclase-activating Polypeptide (PACAP38) in the Adult Mouse Retina : Microglial Activation and Induction of Neural Proliferation}, url = {https://m2.mtmt.hu/api/publication/34074641}, author = {Denes, Viktoria and Lukáts, Ákos and Szarka, Gergely and Subicz, Rovena and Mester, Adrienn and Kovács-Valasek, Andrea and Geck, Peter and Berta, Gergely and Herczeg, Robert and Pöstyéni, Etelka and Gyenesei, Attila and Gábriel, Róbert}, doi = {10.1007/s11064-023-03989-7}, journal-iso = {NEUROCHEM RES}, journal = {NEUROCHEMICAL RESEARCH}, volume = {48}, unique-id = {34074641}, issn = {0364-3190}, abstract = {The degenerative retinal disorders characterized by progressive cell death and exacerbating inflammation lead ultimately to blindness. The ubiquitous neuropeptide, PACAP38 is a promising therapeutic agent as its proliferative potential and suppressive effect on microglia might enable cell replacement and attenuate inflammation, respectively. Our previous finding that PACAP38 caused a marked increase of the amacrine cells in the adult (1-year-old) mouse retina, served as a rationale of the current study. We aimed to determine the proliferating elements and the inflammatory status of the PACAP38-treated retina. Three months old mice were intravitreally injected with 100 pmol PACAP38 at 3 months intervals (3X). Retinas of 1-year-old animals were dissected and effects on cell proliferation, and expression of inflammatory regulators were analyzed. Interestingly, both mitogenic and anti-mitogenic actions were detected after PACAP38-treatment. Further analysis of the mitogenic effect revealed that proliferating cells include microglia, endothelial cells, and neurons of the ganglion cell layer but not amacrine cells. Furthermore, PACAP38 stimulated retinal microglia to polarize dominantly into M2-phenotype but also might cause subsequent angiogenesis. According to our results, PACAP38 might dampen pro-inflammatory responses and help tissue repair by reprogramming microglia into an M2 phenotype, nonetheless, with angiogenesis as a warning side effect.}, keywords = {Inflammation; PROLIFERATION; ANGIOGENESIS; microglia; PACAP38; Adult retina}, year = {2023}, eissn = {1573-6903}, pages = {3430-3446}, orcid-numbers = {Gábriel, Róbert/0000-0001-9323-8795} } @article{MTMT:34074467, title = {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}, url = {https://m2.mtmt.hu/api/publication/34074467}, author = {Fehér, Máté and Márton, Zsombor and Szabó, Ákos and Kocsa, János and Kormos, Viktória and Hunyady, Ágnes and Kovács, László Ákos and Ujvári, Balázs and Berta, Gergely and Farkas, József and Füredi, Nóra and Gaszner, Tamás and Pytel, Bence and Reglődi, Dóra and Gaszner, Balázs}, doi = {10.3390/ijms241411843}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {34074467}, issn = {1661-6596}, abstract = {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.}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Gaszner, Balázs/0000-0003-2830-2732} } @article{MTMT:33937641, title = {Aging Changes the Efficacy of Central Urocortin 2 to Induce Weight Loss in Rats}, url = {https://m2.mtmt.hu/api/publication/33937641}, author = {Kovács, Dóra Krisztina and Eitmann, Szimonetta and Berta, Gergely and Kormos, Viktória and Gaszner, Balázs and Pétervári, Erika and Balaskó, Márta}, doi = {10.3390/ijms24108992}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {33937641}, issn = {1661-6596}, abstract = {Middle-aged obesity and aging cachexia present healthcare challenges. Central responsiveness to body-weight-reducing mediators, e.g., to leptin, changes during aging in a way, which may promote middle-aged obesity and aging cachexia. Leptin is connected to urocortin 2 (Ucn2), an anorexigenic and hypermetabolic member of the corticotropin family. We aimed to study the role of Ucn2 in middle-aged obesity and aging cachexia. The food intake, body weight and hypermetabolic responses (oxygen consumption, core temperature) of male Wistar rats (3, 6, 12 and 18 months) were tested following intracerebroventricular injections of Ucn2. Following one central injection, Ucn2-induced anorexia lasted for 9 days in the 3-month, 14 days in the 6-month and 2 days in the 18-month group. Middle-aged 12-month rats failed to show anorexia or weight loss. Weight loss was transient (4 days) in the 3-month, 14 days in the 6-month and slight but long-lasting in the 18-month rats. Ucn2-induced hypermetabolism and hyperthermia increased with aging. The age-dependent changes in the mRNA expression of Ucn2 detected by RNAscope in the paraventricular nucleus correlated with the anorexigenic responsiveness. Our results show that age-dependent changes in Ucn2 may contribute to middle-aged obesity and aging cachexia. Ucn2 shows potential in the prevention of middle-aged obesity.}, keywords = {OBESITY; Aging; Weight Loss; Metabolic rate; Urocortin 2}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Kovács, Dóra Krisztina/0000-0001-5152-2069; Gaszner, Balázs/0000-0003-2830-2732; Pétervári, Erika/0000-0002-3673-8491} } @article{MTMT:33788449, title = {A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines}, url = {https://m2.mtmt.hu/api/publication/33788449}, author = {Brandt, Barbara and Németh, Marica and Berta, Gergely and Szünstein, Máté and Heffer, Marija and Rauch, Tibor and Pap, Marianna}, doi = {10.3390/ijms24097929}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {24}, unique-id = {33788449}, issn = {1661-6596}, abstract = {There is no effective therapy for the lately increased incidence of glioblastoma multiforme (GBM)—the most common primary brain tumor characterized by a high degree of invasiveness and genetic heterogeneity. Currently, DNA alkylating agent temozolomide (TMZ) is the standard chemotherapy. Nevertheless, TMZ resistance is a major problem in the treatment of GBM due to numerous molecular mechanisms related to DNA damage repair, epigenetic alterations, cellular drug efflux, apoptosis-autophagy, and overactive protein neddylation. Low molecular weight inhibitors of NEDD8-activating enzyme (NAE), such as MLN4924, attenuate protein neddylation and present a promising low-toxicity anticancer agent. The aim of our study was to find an effective combination treatment with TMZ and MLN4924 in our TMZ-resistant GBM cell lines and study the effect of these combination treatments on different protein expressions such as O6-methylguanine methyltransferase (MGMT) and p53. The combination treatment successfully decreased cell viability and sensitized TMZ-resistant cells to TMZ, foreshadowing a new treatment strategy for GBM.}, year = {2023}, eissn = {1422-0067}, orcid-numbers = {Heffer, Marija/0000-0001-6770-7359} } @article{MTMT:33775153, title = {Absence of Nkx2-3 induces ectopic lymphatic endothelial differentiation associated with impaired extramedullary stress hematopoiesis in the spleen.}, url = {https://m2.mtmt.hu/api/publication/33775153}, author = {Gábris, Fanni and Kiss, Gabriella and Szirmay, Balázs and Szomor, Árpád and Berta, Gergely and Jakus, Zoltán and Kellermayer, Zoltán and Balogh, Péter}, doi = {10.3389/fcell.2023.1170389}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {11}, unique-id = {33775153}, issn = {2296-634X}, abstract = {The red and white pulps as two main parts of the spleen are arranged around distinct types of vasculature, and perform significantly different functions in both humans and mice. Previous observations indicated a profound alteration of the local vessel specialization in mice lacking Nkx2-3 homeodomain transcription factor, including contradictory results suggesting presence of an ectopic lymphatic vascular structure. Furthermore, how the absence of Nkx2-3 and the consequential changes in endothelial components affect the extramedullary hematopoietic activity restricted to the splenic red pulp is unknown. In this work, we investigated the role of Nkx2-3 homeodomain transcription factor as a major morphogenic determinant for vascular specification, and its effect in the extramedullary hematopoiesis following acute blood loss and pharmacological stimulation of megakaryocyte differentiation after treatment with thrombopoietin-receptor mimetic Romiplostim. We found that, in mice lacking Nkx2-3, Prox1-positive lymphatic capillaries containing gp38/CD31 double positive lymphatic endothelial cells develop, arranged into an extensive meshwork, while the Clever1-positive venous segments of red pulp blood vasculature are absent. This lymphatic endothelial shift is coupled with a severely compromised splenic erythropoiesis and a significantly reduced splenic megakaryocyte colony formation following Romiplostim treatment in mice lacking Nkx2-3. These findings indicate that the shift of microvascular patterning in the absence of Nkx2-3 includes the emergence of ectopic Prox1-positive lymphatic vessels, and that this pivoting towards lymph node-like vascular patterning is associated with an impaired reserve hematopoietic capacity of the splenic red pulp.}, keywords = {SPLEEN; stroma; Hematopoiesis; Prox1; Nkx2-3; Lymphatic endothelium}, year = {2023}, eissn = {2296-634X}, orcid-numbers = {Gábris, Fanni/0000-0002-6036-3941; Jakus, Zoltán/0000-0002-6304-2369} } @article{MTMT:33728557, title = {Urocortin stimulates the ERK1/2 signaling pathway and the proliferation of HeLa cells via CRF receptor 1}, url = {https://m2.mtmt.hu/api/publication/33728557}, author = {Balogh, Bálint and Vecsernyés, Mónika and Stayer-Harci, Alexandra and Berta, Gergely and Tarjányi, Oktávia and Sétáló, György (ifj.)}, doi = {10.1002/2211-5463.13602}, journal-iso = {FEBS OPEN BIO}, journal = {FEBS OPEN BIO}, volume = {13}, unique-id = {33728557}, issn = {2211-5463}, abstract = {Corticotropin-releasing factor (CRF) stimulates adrenocorticotropic hormone (ACTH) secretion from the pituitary gland and is an essential regulator of the hypothalamic-pituitary-adrenocortical axis. Isoforms of CRF receptor are known to mediate the effects of urocortin stress ligands on the regulation of stress responses, anxiety, and feeding behavior; however, urocortin stress ligands also influence cell proliferation. In view of the tumor-promoting capacity of prolonged stress, here we investigated (a) the effect of urocortin on cell proliferative signaling via extracellular signal-regulated kinase 1/2, (b) the expression and cellular distribution of the specific CRF receptor isoforms, and (c) the intracellular localization of phosphorylated ERK1/2 in HeLa cells. Stimulation of cell proliferation was observed in the presence of 10 nm urocortin. Our data also suggest that MAP kinase MEK, the transcription factors E2F-1 and p53, and PKB/Akt are involved in this process. These findings may have therapeutic relevance for the targeted treatment of various malignancies.}, keywords = {cell proliferation; urocortin; HeLa; E2F-1; ERK1/2, MEK}, year = {2023}, eissn = {2211-5463}, pages = {818-832} } @article{MTMT:33553138, title = {Functionally active TRPA1 ion channel is downregulated in peptidergic neurons of the Edinger-Westphal nucleus upon acute alcohol exposure}, url = {https://m2.mtmt.hu/api/publication/33553138}, author = {Al-omari, Ammar and Kecskés, Miklós and Gaszner, Balázs and Biró-Sütő, Tünde and Fazekas, Balázs and Berta, Gergely and Kuzma, Mónika and Pintér, Erika and Kormos, Viktória}, doi = {10.3389/fcell.2022.1046559}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {10}, unique-id = {33553138}, issn = {2296-634X}, abstract = {Introduction: The centrally projecting Edinger-Westphal nucleus (EWcp) contributes to the control of alcohol consumption by its urocortin 1 (UCN1) and cocaine- and amphetamine-regulated transcript (CART) co-expressing peptidergic neurons. Our group recently showed that the urocortinergic centrally projecting EWcp is the primary seat of central nervous system transient receptor potential ankyrin 1 (TRPA1) cation channel mRNA expression. Here, we hypothesized that alcohol and its metabolites, that pass through the blood-brain barrier, may influence the function of urocortinergic cells in centrally projecting EWcp by activating TRPA1 ion channels. We aimed to examine the functional activity of TRPA1 in centrally projecting EWcp and its possible role in a mouse model of acute alcohol exposure.}, year = {2023}, eissn = {2296-634X}, orcid-numbers = {Gaszner, Balázs/0000-0003-2830-2732; Pintér, Erika/0000-0001-9898-632X} } @article{MTMT:33362860, title = {Effect of pre-heating on the monomer elution and porosity of conventional and bulk-fill resin-based dental composites}, url = {https://m2.mtmt.hu/api/publication/33362860}, author = {Dunavári, Erika Katalin and Berta, Gergely and Kiss, Tamás and Szalma, József and Fráter, Márk Tibor and Böddi, Katalin and Lempel, Edina}, doi = {10.3390/ijms232416188}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33362860}, issn = {1661-6596}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Szalma, József/0000-0002-6006-8758; Fráter, Márk Tibor/0000-0002-0365-1613} }