TY - JOUR AU - Hakkel, Erzsébet AU - Varga, Edina AU - Kovács, Balázs AU - Stiftné Szilvásy-Szabó, Anett AU - Cote-Vélez, Antonieta AU - Péterfi, Zoltán Attila AU - Matziari, Magdalini AU - Tóth, Mónika AU - Zelena, Dóra AU - Mezriczky, Zsolt AU - Kádár, Andrea AU - Kővári, Dóra AU - Watanabe, Masahiko AU - Kano, Masanobu AU - Mackie, Ken AU - Rózsa J., Balázs AU - Ruska, Yvette Magdolna AU - Tóth, Blanka AU - Máté, Zoltán AU - Erdélyi, Ferenc AU - Szabó, Gábor AU - Gereben, Balázs AU - Lechan, Ronald M. AU - Charli, Jean-Louis AU - Joseph-Bravo, Patricia AU - Fekete, Csaba TI - A glial-neuronal circuit in the median eminence regulates thyrotropin-releasing hormone-release via the endocannabinoid system. JF - ISCIENCE J2 - ISCIENCE VL - 23 PY - 2020 IS - 3 PG - 41 SN - 2589-0042 DO - 10.1016/j.isci.2020.100921 UR - https://m2.mtmt.hu/api/publication/31183722 ID - 31183722 N1 - * Megosztott szerzőség LA - English DB - MTMT ER - TY - JOUR AU - Varga, Edina AU - Hakkel, Erzsébet AU - Zséli, Györgyi AU - Kádár, Andrea AU - Venczel, Alexandra AU - Kővári, Dóra AU - Németh, Dorottya AU - Máté, Zoltán AU - Erdélyi, Ferenc AU - Horváth, András AU - Szenci, Ottó AU - Watanabe, Masahiko AU - Lechan, Ronald M AU - Gereben, Balázs AU - Fekete, Csaba TI - Thyrotropin-Releasing-Hormone-Synthesizing Neurons of the Hypothalamic Paraventricular Nucleus Are Inhibited by Glycinergic Inputs JF - THYROID J2 - THYROID VL - 29 PY - 2019 IS - 12 SP - 1858 EP - 1868 PG - 11 SN - 1050-7256 DO - 10.1089/thy.2019.0357 UR - https://m2.mtmt.hu/api/publication/31014345 ID - 31014345 N1 - Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Medical Gene Technology Unit, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Department and Clinic for Production Animals, University of Veterinary Medicine Budapest, Üllő, Dóra Major, Hungary MTA–SZIE Large Animal Clinical Research Group, Üllő, Dóra major, Hungary Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Japan Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Tupper Research Institute, Tufts Medical Center, Boston, MA, United States Department of Neuroscience, Tufts University School of Medicine, Boston, MA, United States Cited By :2 Export Date: 3 February 2023 CODEN: THYRE Correspondence Address: Fekete, C.; Department of Endocrine Neurobiology, Hungary; email: fekete.csaba@koki.mta.hu Chemicals/CAS: glycine, 56-40-6, 6000-43-7, 6000-44-8; protirelin, 24305-27-9; strychnine, 1421-86-9, 57-24-9; tetrodotoxin, 4368-28-9, 4664-41-9; Glycine; Glycine Plasma Membrane Transport Proteins; Receptors, Glycine; Slc6a5 protein, mouse; Tetrodotoxin; Thyrotropin-Releasing Hormone Funding details: 666869 Funding details: 2017-1.2.1-NKP-2017-00002 Funding details: K124767 Funding details: Hungarian Scientific Research Fund, OTKA Funding details: Universität Zürich, UZH Funding details: Hungarian Science Foundation Funding text 1: This work was supported by Grants from the Hungarian Science Foundation (OTKA K124767), the Hungarian National Brain Research Program (2017-1.2.1-NKP-2017-00002) and EU H2020 THYRAGE no. 666869. Funding text 2: The authors are very grateful to Dr. Hanns Ulrich Zeilhofer (University of Zurich, Zurich, Switzerland) for the kind gift of GLYT2::GFP and GLYT2::Cre mice. This work was supported by Grants from the Hungarian Science Foundation (OTKA K124767), the Hungarian National Brain Research Program (2017-1.2.1-NKP-2017-00002) and EU H2020 THYRAGE no. 666869. AB - Background: Glycine is a classical neurotransmitter that has role in both inhibitory and excitatory synapses. To understand whether glycinergic inputs are involved in the regulation of the hypophysiotropic thyrotropin-releasing hormone (TRH) neurons, the central controllers of the hypothalamic-pituitary-thyroid axis, the glycinergic innervation of the TRH neurons was studied in the hypothalamic paraventricular nucleus (PVN). Methods: Double-labeling immunocytochemistry and patch-clamp electrophysiology were used to determine the role of glycinergic neurons in the regulation of TRH neurons in the PVN. Anterograde and retrograde tracing methods were used to determine the sources of the glycinergic input of TRH neurons. Results: Glycine transporter-2 (GLYT2), a marker of glycinergic neurons, containing axons were found to establish symmetric type of synapses on TRH neurons in the PVN. Furthermore, glycine receptor immunoreactivity was observed in these TRH neurons. The raphe magnus (RMg) and the ventrolateral periaqueductal gray (VLPAG) were found to be the exclusive sources of the glycinergic innervation of the TRH neurons within the PVN. Patch-clamp electrophysiology using sections of TRH-IRES-tdTomato mice showed that glycine hyperpolarized the TRH neurons and completely blocked the firing of these neurons. Glycine also markedly hyperpolarized the TRH neurons in the presence of tetrodotoxin demonstrating the direct effect of glycine. In more than 60% of the TRH neurons, spontaneous inhibitory postsynaptic currents (sIPSCs) were observed, even after the pharmacological inhibition of glutamatergic and GABAergic neuronal transmission. The glycine antagonist, strychnine, almost completely abolished these sIPSCs, demonstrating the inhibitory nature of the glycinergic input of TRH neurons. Conclusions: These data demonstrate that TRH neurons in the PVN receive glycinergic inputs from the RMg and the VLPAG. The symmetric type of synaptic connection and the results of the electrophysiological experiments demonstrate the inhibitory nature of these inputs. LA - English DB - MTMT ER - TY - JOUR AU - Stiftné Szilvásy-Szabó, Anett AU - Varga, Edina AU - Beliczai, Z AU - Lechan, RM AU - Fekete, Csaba TI - Localization of connexin 43 gap junctions and hemichannels in tanycytes of adult mice JF - BRAIN RESEARCH J2 - BRAIN RES VL - 1673 PY - 2017 SP - 64 EP - 71 PG - 8 SN - 0006-8993 DO - 10.1016/j.brainres.2017.08.010 UR - https://m2.mtmt.hu/api/publication/3273250 ID - 3273250 N1 - Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Semmelweis University Neurosciences Doctoral School, Neuroendocrinology Program, Budapest, Hungary Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA, United States Department of Neuroscience, Tufts University School of Medicine, Boston, MA, United States Cited By :8 Export Date: 3 February 2021 CODEN: BRREA Correspondence Address: Fekete, C.; Department of Endocrine Neurobiology, 43 Szigony St., Hungary; email: fekete.csaba@koki.mta.hu Chemicals/CAS: lucifer yellow, 67769-47-5, 82446-52-4; carbenoxolone, 5697-56-3, 7421-40-1; Carbenoxolone; Central Nervous System Agents; Connexin 43; GJA1 protein, mouse; Vimentin Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary Semmelweis University Neurosciences Doctoral School, Neuroendocrinology Program, Budapest, Hungary Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, MA, United States Department of Neuroscience, Tufts University School of Medicine, Boston, MA, United States Cited By :8 Export Date: 4 February 2021 CODEN: BRREA Correspondence Address: Fekete, C.; Department of Endocrine Neurobiology, 43 Szigony St., Hungary; email: fekete.csaba@koki.mta.hu Chemicals/CAS: lucifer yellow, 67769-47-5, 82446-52-4; carbenoxolone, 5697-56-3, 7421-40-1; Carbenoxolone; Central Nervous System Agents; Connexin 43; GJA1 protein, mouse; Vimentin AB - Tanycytes are specialized glial cells lining the lateral walls and the floor of the third ventricle behind the optic chiasm. In addition to functioning as barrier cells, they also have an important role in the regulation of neuroendocrine axes and energy homeostasis. To determine whether tanycytes communicate with each other via Connexin 43 (Cx43) gap junctions, individual tanycytes were loaded with Lucifer yellow (LY) through a patch pipette. In all cases, LY filled a larger group of tanycytes as well as blood vessels adjacent to tanycyte processes. The Cx43-blocker, carbenoxolone, inhibited spreading of LY. The greatest density of Cx43-immunoreactive spots was observed in the cell membrane of alpha-tanycyte cell bodies. Cx43-immunoreactivity was also present in the membrane of beta-tanycyte cell bodies, but in lower density. Processes of both types of tanycytes also contained Cx43-immunoreactivity. At the ultrastructural level, Cx43-immunoreactivity was present in the cell membrane of all types of tanycytes including their ventricular surface, but gap junctions were more frequent among alpha-tanycytes. Cx43-immunoreactivity was also observed in the cell membrane between contacting tanycyte endfeet processes, and between tanycyte endfeet process and axon varicosities in the external zone of the median eminence and capillaries in the arcuate nucleus and median eminence. These results suggest that gap junctions are present not only among tanycytes, but also between tanycytes and the axons of hypophysiotropic neurons. Cx43 hemichannels may also facilitate the transport between tanycytes and extracellular fluids, including the cerebrospinal fluid, extracellular space of the median eminence and bloodstream. LA - English DB - MTMT ER - TY - THES AU - Varga, Edina TI - Abeta(1-42) enhances neuronal excitability and disrupts synaptic plasticity by altering glutamate recycling PB - Szegedi Tudományegyetem (SZTE) PY - 2015 SP - 67 DO - 10.14232/phd.2588 UR - https://m2.mtmt.hu/api/publication/3027471 ID - 3027471 LA - English DB - MTMT ER - TY - JOUR AU - Varga, Edina AU - Juhász, Gábor AU - Bozsó, Zsolt AU - Penke, Botond AU - Fülöp, Lívia AU - Szegedi, Viktor TI - Amyloid-β1-42 disrupts synaptic plasticity by altering glutamate recycling at the synapse JF - JOURNAL OF ALZHEIMER'S DISEASE J2 - J ALZHEIMERS DIS VL - 45 PY - 2015 IS - 2 SP - 449 EP - 456 PG - 8 SN - 1387-2877 DO - 10.3233/JAD-142367 UR - https://m2.mtmt.hu/api/publication/2812783 ID - 2812783 AB - Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders characterized by neuritic plaques containing amyloid-beta peptide (Abeta) and neurofibrillary tangles. Evidence has been reported that Abeta1-42 plays an essential pathogenic role in decreased spine density, impairment of synaptic plasticity, and neuronal loss with disruption of memory-related synapse function, all associated with AD. Experimentally, Abeta1-42 oligomers perturb hippocampal long-term potentiation (LTP), an electrophysiological correlate of learning and memory. Abeta was also reported to perturb synaptic glutamate (Glu)-recycling by inhibiting excitatory-amino-acid-transporters. Elevated level of extracellular Glu leads to activation of perisynaptic receptors, including NR2B subunit containing NMDARs. These receptors were shown to induce impaired LTP and enhanced long-term depression and proapoptotic pathways, all central features of AD. In the present study, we investigated the role of Glu-recycling on Abeta1-42-induced LTP deficit in the CA1. We found that Abeta-induced LTP damage, which was mimicked by the Glu-reuptake inhibitor TBOA, could be rescued by blocking the NR2B subunit of NMDA receptors. Furthermore, decreasing the level of extracellular Glu using a Glu scavenger also restores TBOA or Abeta induces LTP damage. Overall, these results suggest that reducing ambient Glu in the brain can be protective against Abeta-induced synaptic disruption. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Edina AU - Juhász, Gábor AU - Bozsó, Zsolt AU - Penke, Botond AU - Fülöp, Lívia AU - Szegedi, Viktor TI - Abeta(1-42) Enhances Neuronal Excitability in the CA1 via NR2B Subunit-Containing NMDA Receptors JF - NEURAL PLASTICITY J2 - NEURAL PLAST VL - 2014 PY - 2014 PG - 12 SN - 2090-5904 DO - 10.1155/2014/584314 UR - https://m2.mtmt.hu/api/publication/2755870 ID - 2755870 AB - Neuronal hyperexcitability is a phenomenon associated with early Alzheimer's disease. The underlying mechanism is considered to involve excessive activation of glutamate receptors; however, the exact molecular pathway remains to be determined. Extracellular recording from the CA1 of hippocampal slices is a long-standing standard for a range of studies both in basic research and in neuropharmacology. Evoked field potentials (fEPSPs) are regarded as the input, while spiking rate is regarded as the output of the neuronal network; however, the relationship between these two phenomena is not fully clear. We investigated the relationship between spontaneous spiking and evoked fEPSPs using mouse hippocampal slices. Blocking AMPA receptors (AMPARs) with CNQX abolished fEPSPs, but left firing rate unchanged. NMDA receptor (NMDAR) blockade with MK801 decreased neuronal spiking dose dependently without altering fEPSPs. Activating NMDARs by small concentration of NMDA induced a trend of increased firing. These results suggest that fEPSPs are mediated by synaptic activation of AMPARs, while spontaneous firing is regulated by the activation of extrasynaptic NMDARs. Synaptotoxic Abeta(1-42) increased firing activity without modifying evoked fEPSPs. This hyperexcitation was prevented by ifenprodil, an antagonist of the NR2B NMDARs. Overall, these results suggest that Abeta(1-42) induced neuronal overactivity is not dependent on AMPARs but requires NR2B. 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 -