TY - JOUR AU - Dócs, Klaudia AU - Balázs, Anita AU - Papp, Ildikó AU - Szűcs, Péter AU - Hegyi, Zoltán TI - Reactive spinal glia convert 2-AG to prostaglandins to drive aberrant astroglial calcium signaling JF - FRONTIERS IN CELLULAR NEUROSCIENCE J2 - FRONT CELL NEUROSCI VL - 18 PY - 2024 PG - 17 SN - 1662-5102 DO - 10.3389/fncel.2024.1382465 UR - https://m2.mtmt.hu/api/publication/34857224 ID - 34857224 N1 - Edited by: Renato Socodato, University of Porto, Portugal Reviewed by: - Robert Kraft, Leipzig University, Germany - Francesco Ferrini, University of Turin, Italy - Marcello Melone, Marche Polytechnic University, Italy AB - The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) influences neurotransmission in the central nervous system mainly by activating type 1 cannabinoid receptor (CB1). Following its release, 2-AG is broken down by hydrolases to yield arachidonic acid, which may subsequently be metabolized by cyclooxygenase-2 (COX-2). COX-2 converts arachidonic acid and also 2-AG into prostanoids, well-known inflammatory and pro-nociceptive mediators. Here, using immunohistochemical and biochemical methods and pharmacological manipulations, we found that reactive spinal astrocytes and microglia increase the expression of COX-2 and the production of prostaglandin E2 when exposed to 2-AG. Both 2-AG and PGE2 evoke calcium transients in spinal astrocytes, but PGE2 showed 30% more efficacy and 55 times more potency than 2-AG. Unstimulated spinal dorsal horn astrocytes responded to 2-AG with calcium transients mainly through the activation of CB1. 2-AG induced exaggerated calcium transients in reactive astrocytes, but this increase in the frequency and area under the curve of calcium signals was only partially dependent on CB1. Instead, aberrant calcium transients were almost completely abolished by COX-2 inhibition. Our results suggest that both reactive spinal astrocytes and microglia perform an endocannabinoid-prostanoid switch to produce PGE2 at the expense of 2-AG. PGE2 in turn is responsible for the induction of aberrant astroglial calcium signals which, together with PGE2 production may play role in the development and maintenance of spinal neuroinflammation-associated disturbances such as central sensitization. LA - English DB - MTMT ER - TY - CHAP AU - Aszalósné Balogh, Rebeka AU - Lőkös, László AU - Adorján, Balázs AU - Freytag, Csongor AU - Mészáros, Ilona AU - Oláh, Viktor AU - Szűcs, Péter AU - Erzberger, Peter AU - Farkas, Edit AU - Matus, Gábor ED - Buró, Botond ED - Molnár, Mihály TI - Városi lapostetők mint kriptogám élőhelyek T2 - XIX. Kárpát-medencei Környezettudományi Konferencia. Absztrakt füzet PB - MTA Atommagkutató Intézet CY - Debrecen SN - 9789638321602 T3 - Kárpát-Medencei Környezettudományi Konferencia, ISSN 1842-9815 PY - 2024 SP - 104 EP - 105 PG - 2 UR - https://m2.mtmt.hu/api/publication/34801279 ID - 34801279 LA - English DB - MTMT ER - TY - JOUR AU - Safronov, Boris V. AU - Szűcs, Péter TI - Novel aspects of signal processing in lamina I JF - NEUROPHARMACOLOGY J2 - NEUROPHARMACOLOGY VL - 247 PY - 2024 SP - 109858 SN - 0028-3908 DO - 10.1016/j.neuropharm.2024.109858 UR - https://m2.mtmt.hu/api/publication/34687816 ID - 34687816 LA - English DB - MTMT ER - TY - JOUR AU - Gaspar, Krisztian AU - Somogyi, Orsolya AU - Dajnoki, Zsolt AU - Szabó, Lilla AU - Hendrik, Zoltán AU - Zouboulis, Christos C. AU - Dócs, Klaudia AU - Szűcs, Péter AU - Dull, Katalin AU - Törőcsik, Dániel AU - Kapitány, Anikó AU - Szegedi, Andrea TI - Skin barrier alterations are not a characteristic feature of hidradenitis suppurativa JF - EXPERIMENTAL DERMATOLOGY J2 - EXP DERMATOL VL - 32 PY - 2023 IS - Supplement_1 SP - 45 EP - 45 PG - 1 SN - 0906-6705 UR - https://m2.mtmt.hu/api/publication/34693588 ID - 34693588 LA - English DB - MTMT ER - TY - JOUR AU - Csemer , Andrea AU - Kovács, Adrienn AU - Maamrah, Baneen AU - Deák-Pocsai, Krisztina AU - Korpás, Kristóf Levente AU - Klekner, Álmos AU - Szűcs, Péter AU - Nánási, Péter Pál AU - Pál, Balázs Zoltán TI - Astrocyte- and NMDA receptor-dependent slow inward currents differently contribute to synaptic plasticity in an age-dependent manner in mouse and human neocortex JF - AGING CELL J2 - AGING CELL VL - 22 PY - 2023 IS - 9 PG - 19 SN - 1474-9718 DO - 10.1111/acel.13939 UR - https://m2.mtmt.hu/api/publication/34085014 ID - 34085014 N1 - e13939 ACE-22-0862.R1 AB - Slow inward currents (SICs) are known as excitatory events of neurons elicited by astrocytic glutamate via activation of extrasynaptic NMDA receptors. By using slice electrophysiology, we tried to provide evidence that SICs can elicit synaptic plasticity. Age dependence of SICs and their impact on synaptic plasticity was also investigated in both on murine and human cortical slices. It was found that SICs can induce a moderate synaptic plasticity, with features similar to spike timing-dependent plasticity. Overall SIC activity showed a clear decline with aging in humans and completely disappeared above a cutoff age. In conclusion, while SICs contribute to a form of astrocyte-dependent synaptic plasticity both in mice and humans, this plasticity is differentially affected by aging. Thus, SICs are likely to play an important role in age-dependent physiological and pathological alterations of synaptic plasticity. LA - English DB - MTMT ER - TY - JOUR AU - Luz, Liliana L. AU - Lima, Susana AU - Fernandes, Elisabete C. AU - Kókai, Éva AU - Gomori, Lidia AU - Szűcs, Péter AU - Safronov, Boris V. TI - Contralateral Afferent Input to Lumbar Lamina I Neurons as a Neural Substrate for Mirror-Image Pain JF - JOURNAL OF NEUROSCIENCE J2 - J NEUROSCI VL - 43 PY - 2023 IS - 18 SP - 3245 EP - 3258 PG - 14 SN - 0270-6474 DO - 10.1523/JNEUROSCI.1897-22.2023 UR - https://m2.mtmt.hu/api/publication/33947896 ID - 33947896 AB - Mirror-image pain arises from pathologic alterations in the nociceptive processing network that controls functional lateralization of the primary afferent input. Although a number of clinical syndromes related to dysfunction of the lumbar afferent system are associated with the mirror-image pain, its morphophysiological substrate and mechanism of induction remain poorly understood. Therefore, we used ex vivo spinal cord preparation of young rats of both sexes to study organization and processing of the contralateral afferent input to the neurons in the major spinal nociceptive projection area Lamina I. We show that decussating primary afferent branches reach contralateral Lamina I, where 27% of neurons, including projection neurons, receive monosynaptic and/or polysynaptic excitatory drive from the contralateral Aδ-fibers and C-fibers. All these neurons also received ipsilateral input, implying their involvement in the bilateral information processing. Our data further show that the contralateral Aδ-fiber and C-fiber input is under diverse forms of inhibitory control. Attenuation of the afferent-driven presynaptic inhibition and/or disinhibition of the dorsal horn network increased the contralateral excitatory drive to Lamina I neurons and its ability to evoke action potentials. Furthermore, the contralateral Aβδ-fibers presynaptically control ipsilateral C-fiber input to Lamina I neurons. Thus, these results show that some lumbar Lamina I neurons are wired to the contralateral afferent system whose input, under normal conditions, is subject to inhibitory control. A pathologic disinhibition of the decussating pathways can open a gate controlling contralateral information flow to the nociceptive projection neurons and, thus, contribute to induction of hypersensitivity and mirror-image pain. LA - English DB - MTMT ER - TY - JOUR AU - Ducza, László AU - Gajtkó, Andrea AU - Hegedűs, Krisztina AU - Bakk, Erzsébet AU - Kis, Nikoletta Gréta AU - Gaál, Botond Ágoston AU - Takács, Roland Ádám AU - Szűcs, Péter AU - Matesz, Klára AU - Szentesiné Holló, Krisztina TI - Neuronal P2X4 receptor may contribute to peripheral inflammatory pain in rat spinal dorsal horn JF - FRONTIERS IN MOLECULAR NEUROSCIENCE J2 - FRONT MOL NEUROSCI VL - 16 PY - 2023 SN - 1662-5099 DO - 10.3389/fnmol.2023.1115685 UR - https://m2.mtmt.hu/api/publication/33682003 ID - 33682003 AB - Abstract Intense inflammation may result in pain, which manifests as spinal central sensitisation. There is growing evidence that purinergic signaling plays a pivotal role in the orchestration of pain processing. Over the last decade the ionotropic P2X purino receptor 4 (P2X4) got into spotlight in neuropathic disorders, however its precise spinal expression was scantily characterised during inflammatory pain. Thus, we intended to analyse the receptor distribution within spinal dorsal horn and lumbar dorsal root ganglia (DRG) of rats suffering in inflammatory pain induced by complete Freund adjuvant (CFA). Methods CFA- induced peripheral inflammation was validated by mechanical and thermal behavioural tests. In order to ensure about the putative alteration of spinal P2X4 receptor gene expression qPCR reactions were designed, followed by immunoperoxidase and Western blot experiments to assess changes at a protein level. Colocalisation of P2X4 with neuronal and glial markers was investigated by double immunofluorescent labelings, which were subsequently analysed with IMARIS software. Transmission electronmicroscopy was applied to study the ultrastructural localisation of the receptor. Concurrently, in lumbar DRG cells similar methodology has been carried out to complete our observations. Results The figures of mechanical and thermal behavioural tests proved the establishment of CFA- induced inflammatory pain. We observed significant enhancement of P2X4 transcript level within the spinal dorsal horn three days upon CFA administration. Elevation of P2X4 immunoreactivity within Rexed lamina I-II of the spinal gray matter was synchronous with mRNA expression, and confirmed by protein blotting. According to IMARIS analysis the robust protein increase was mainly detected on primary afferent axontermini and GFAP-labelled astrocyte membrane compartments within the spinal dorsal horn, but not on postsynaptic dendrites was also validated ultrastructurally. Furthermore, lumbar DRG analysis demonstrated that peptidergic and non-peptidergic nociceptive subsets of ganglia cells were also abundantly positive for P2X4 receptor in CFA model. Conclusions Here we provide novel evidence about involvement of neuronal and glial P2X4 receptor in the establishment of inflammatory pain. LA - English DB - MTMT ER - TY - JOUR AU - Somogyi, Orsolya AU - Dajnoki, Zsolt AU - Szabó, Lilla AU - Gáspár, Krisztián AU - Hendrik, Zoltán AU - Zouboulis, Christos C. AU - Dócs, Klaudia AU - Szűcs, Péter AU - Dull, Katalin AU - Törőcsik, Dániel AU - Kapitány, Anikó AU - Szegedi, Andrea TI - New Data on the Features of Skin Barrier in Hidradenitis Suppurativa JF - BIOMEDICINES J2 - BIOMEDICINES VL - 11 PY - 2023 IS - 1 PG - 12 SN - 2227-9059 DO - 10.3390/biomedicines11010127 UR - https://m2.mtmt.hu/api/publication/33620531 ID - 33620531 AB - Hidradenitis suppurativa (HS) is a Th1/17-driven inflammatory skin disease of the apocrine gland-rich (AGR) skin regions, where keratinocytes seem to be the crucial drivers of the initial pathogenic steps. However, the possible role of permeability barrier alteration in activating keratinocytes during HS development has not been clarified. We compared the major permeability barrier elements of non-lesional HS (HS-NL; n = 10) and lesional HS (HS-L; n = 10) skin with healthy AGR regions (n = 10) via RT-qPCR and immunohistochemistry. Stratum corneum components related to cornified envelope formation, corneocyte desquamation and (corneo)desmosome organization were analyzed along with tight junction molecules and barrier alarmins. The permeability barrier function was also investigated with transepidermal water loss (TEWL) measurements (n = 16). Junction structures were also visualized using confocal microscopy. At the gene level, none of the investigated molecules were significantly altered in HS-NL skin, while 11 molecules changed significantly in HS-L skin versus control. At the protein level, the investigated molecules were similarly expressed in HS-NL and AGR skin. In HS-L skin, only slight changes were detected; however, differences did not show a unidirectional alteration, as KRT1 and KLK5 were detected in decreased levels, and KLK7, KRT6 and DSG1 in increased levels. No significant differences in TEWL or the expression of junction structures were assessed. Our findings suggest that the permeability barrier is not significantly damaged in HS skin and permeability barrier alterations are not the driver factors of keratinocyte activation in this disease. LA - English DB - MTMT ER - TY - JOUR AU - Kókai, Éva AU - Luz, Lilana L. AU - Fernandes, Elisabete C. AU - Safronov, Boris V AU - Poisbeau, Pierrick AU - Szűcs, Péter TI - Quantitative spatial analysis reveals that the local axons of lamina I projection neurons and interneurons exhibit distributions that predict distinct roles in spinal sensory processing JF - JOURNAL OF COMPARATIVE NEUROLOGY J2 - J COMP NEUROL VL - 530 PY - 2022 IS - 18 SP - 3270 EP - 3287 PG - 18 SN - 0021-9967 DO - 10.1002/cne.25413 UR - https://m2.mtmt.hu/api/publication/33174596 ID - 33174596 AB - Our knowledge about the detailed wiring of neuronal circuits in the spinal dorsal horn (DH), where initial sensory processing takes place, is still very sparse. While a substantial amount of data is available on the somatodendritic morphology of DH neurons, the laminar and segmental distribution patterns and consequential function of individual axons are much less characterized. In the present study, we fully reconstructed the axonal and dendritic processes of 10 projection neurons (PNs) and 15 interneurons (INs) in lamina I of the rat, to reveal quantitative differences in their distribution. We also performed whole-cell patch-clamp recordings to test the predicted function of certain axon collaterals. In line with our earlier qualitative description, we found that lamina I INs in the lateral aspect of the superficial DH send axon collaterals toward the medial part and occupy mostly laminae I-III, providing anatomical basis for a lateromedial flow of information within the DH. Local axon collaterals of PNs were more extensively distributed including dorsal commissural axon collaterals that might refer to those reported earlier linking the lateral aspect of the left and right DHs. PN collaterals dominated the dorsolateral funiculus and laminae IV-VI, suggesting propriospinal and ventral connections. Indeed, patch-clamp recordings confirmed the existence of a dorsoventral excitatory drive upon activation of neurokinin-1 receptors that, although being expressed in various lamina I neurons, are specifically enriched in PNs. In summary, lamina I PNs and INs have almost identical dendritic input fields, while their segmental axon collateral distribution patterns are distinct. INs, whose somata reside in lamina I, establish local connections, may show asymmetry, and contribute to bridging the medial and lateral halves of the DH. PNs, on the other hand, preferably relay their integrated dendritic input to deeper laminae of the spinal gray matter where it might be linked to other ascending pathways or the premotor network, resulting in a putative direct contribution to the nociceptive withdrawal reflex. LA - English DB - MTMT ER - TY - JOUR AU - Papp, Tamás AU - Ferenczi, Zsuzsanna AU - Szilagyi, Bernadette AU - Petro, Matyas AU - Varga, Angelika AU - Kókai, Éva AU - Berényi, Ervin László AU - Oláh, Gábor AU - Halmos, Gábor AU - Szűcs, Péter AU - Mészár, Zoltán TI - Ultrasound Used for Diagnostic Imaging Facilitates Dendritic Branching of Developing Neurons in the Mouse Cortex JF - FRONTIERS IN NEUROSCIENCE J2 - FRONT NEUROSCI-SWITZ VL - 16 PY - 2022 SN - 1662-4548 DO - 10.3389/fnins.2022.803356 UR - https://m2.mtmt.hu/api/publication/32769720 ID - 32769720 N1 - Department of Medical Imaging, University of Debrecen, Debrecen, Hungary Department of Anatomy, Histology and Embryology, University of Debrecen, Debrecen, Hungary Department of Biopharmacy, University of Debrecen, Debrecen, Hungary MTA-Debreceni Egyetem, Neuroscience Research Group, Debrecen, Hungary Export Date: 18 January 2023 Correspondence Address: Papp, T.; Department of Medical Imaging, Hungary; email: papp.tamas@med.unideb.hu Funding details: 2017-1.2.1-NKP-00002, TKP2021-EGA-20 Funding text 1: This work was supported by the National Brain Project of Hungary (NAP2, 2017-1.2.1-NKP-00002) to ZM and PS and by the Thematic Excellence Programme TKP2021-EGA-20 (Biotechnology) of the Ministry for Innovation and Technology in Hungary to GH as well as by the UD Faculty of Medicine Research Fund (Bridging Fund) to AV. LA - English DB - MTMT ER -