TY - JOUR AU - Kollai, Sarolta AU - Bereczki, Dániel AU - Glasz, Tibor AU - Hortobágyi, Tibor AU - Kovács, Tibor TI - Early histopathological changes of secondary degeneration in the spinal cord after total MCA territory stroke JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 9 SN - 2045-2322 DO - 10.1038/s41598-023-49230-x UR - https://m2.mtmt.hu/api/publication/34441451 ID - 34441451 LA - English DB - MTMT ER - TY - JOUR AU - Faragó, Péter AU - Kincses, Zsigmond Tamás AU - Kovács, László AU - Hortobágyi, Tibor AU - Despotov, Katalin AU - Radics, Bence AU - Klivényi, Péter AU - Tajti, János TI - Isolated IgG4 hypertrophic pachymeningitis with cranial nerve involvement [Izolált IgG4 hypertrophiás pachymeningitis agyideg-érintettséggel]. [case report] TS - [case report] JF - IDEGGYOGYASZATI SZEMLE / CLINICAL NEUROSCIENCE J2 - IDEGGYOGY SZEMLE VL - 76 PY - 2023 IS - 1-2 SP - 58 EP - 62 PG - 5 SN - 0019-1442 DO - 10.18071/isz.76.0058 UR - https://m2.mtmt.hu/api/publication/33692419 ID - 33692419 N1 - Szövegében 3 oldalnál rövidebb esetismertetés, ezért besorolása rövid közlemény az MTA V. Osztályának ajánlása alapján. (SE, SZTE admin5, 2023-09-22) AB - IgG4-related (IgG4-RD) disease is a relatively newly identified, chronic autoimmune disorder that can affect any organ system. The disease is relatively rare. It has mostly systemic presentation, however it can also appear in isolated form in one single organ. In our report, we demonstrate an elderly male patient’s case with IgG4-RD presented in the form of diffuse meningeal inflammation and hypertrophic pachymeningitis with one-sided cranial nerve and intraventricular involvement. LA - English DB - MTMT ER - TY - JOUR AU - Glebov, Oleg O. AU - Williamson, David AU - Owen, Dylan M. AU - Hortobágyi, Tibor AU - Troakes, Claire AU - Aarsland, Dag TI - Structural synaptic signatures of Alzheimer's disease and dementia with Lewy bodies in the male brain JF - NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY J2 - NEUROPATH APPL NEURO VL - 49 PY - 2023 IS - 1 SN - 0305-1846 DO - 10.1111/nan.12852 UR - https://m2.mtmt.hu/api/publication/33219396 ID - 33219396 LA - English DB - MTMT ER - TY - JOUR AU - Fehér, Ádám AU - Pethő, Zoltán Dénes AU - Szántó, Gábor Tibor AU - Klekner, Álmos AU - Tajti, Gábor AU - Batta, Gyula Gábor (Ifj.) AU - Hortobágyi, Tibor AU - Varga, Zoltán AU - Schwab, Albrecht AU - Panyi, György TI - Mapping the functional expression of auxiliary subunits of KCa1.1 in glioblastoma JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 14 SN - 2045-2322 DO - 10.1038/s41598-022-26196-w UR - https://m2.mtmt.hu/api/publication/33398474 ID - 33398474 AB - Glioblastoma (GBM) is the most aggressive glial tumor, where ion channels, including K Ca 1.1, are candidates for new therapeutic options. Since the auxiliary subunits linked to K Ca 1.1 in GBM are largely unknown we used electrophysiology combined with pharmacology and gene silencing to address the functional expression of K Ca 1.1/ β subunits complexes in both primary tumor cells and in the glioblastoma cell line U-87 MG. The pattern of the sensitivity (activation/inhibition) of the whole-cell currents to paxilline, lithocholic acid, arachidonic acid, and iberiotoxin; the presence of inactivation of the whole-cell current along with the loss of the outward rectification upon exposure to the reducing agent DTT collectively argue that K Ca 1.1/β3 complex is expressed in U-87 MG. Similar results were found using human primary glioblastoma cells isolated from patient samples. Silencing the β3 subunit expression inhibited carbachol-induced Ca 2+ transients in U-87 MG thereby indicating the role of the K Ca 1.1/β3 in the Ca 2+ signaling of glioblastoma cells. Functional expression of the K Ca 1.1/β3 complex, on the other hand, lacks cell cycle dependence. We suggest that the K Ca 1.1/β3 complex may have diagnostic and therapeutic potential in glioblastoma in the future. LA - English DB - MTMT ER - TY - CHAP AU - Gebri, Enikő AU - Tóth, Ferenc AU - Szarka, Máté AU - Nemes, Balázs AU - Varga, István AU - Hortobágyi, Tibor TI - Vesetranszplantáció fogászati vonatkozásai T2 - XXII. Debreceni Fogászati Napok PB - Debreceni Egyetem CY - Debrecen SN - 9789634904250 PY - 2022 SP - 54 UR - https://m2.mtmt.hu/api/publication/33340885 ID - 33340885 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Varkoly, Gréta AU - Hortobágyi, Tibor G. AU - Gebri, Enikő AU - Bencze, János AU - Hortobágyi, Tibor AU - Módis, László TI - Expression Pattern of Tenascin-C, Matrilin-2, and Aggrecan in Diseases Affecting the Corneal Endothelium JF - JOURNAL OF CLINICAL MEDICINE J2 - J CLIN MED VL - 11 PY - 2022 IS - 20 PG - 19 SN - 2077-0383 DO - 10.3390/jcm11205991 UR - https://m2.mtmt.hu/api/publication/33216597 ID - 33216597 AB - Purpose: The aim of this study was to examine the expression pattern of tenascin-C, matrilin-2, and aggrecan in irreversible corneal endothelial pathology such as pseudophakic bullous keratopathy (PBK) and Fuchs’ endothelial corneal dystrophy (FECD), which most frequently require corneal transplantation. Materials and methods: Histological specimens of corneal buttons removed during keratoplasty were investigated in PBK (n = 20) and FECD (n = 9) and compared to healthy control corneas (n = 10). The sections were studied by chromogenic immunohistochemistry (CHR-IHC) and submitted for evaluation by two investigators. Semiquantitative scoring (0 to 3+) was applied according to standardized methods at high magnification (400x). Each layer of the cornea was investigated; in addition, the stroma was subdivided into anterior, middle, and posterior parts for more precise analysis. In case of non-parametric distribution Mann–Whitney test was applied to compare two groups. Kruskal–Wallis and Dunn’s multiple comparisons tests have been applied for comparison of the chromogenic IHC signal intensity among corneal layers within the control and patient groups. Differences of p < 0.05 were considered as significant. Results: Significantly elevated tenascin-C immunopositivity was present in the epithelium and every layer of the stroma in both pathologic conditions as compared to normal controls. In addition, also significantly stronger matrilin-2 positivity was detected in the epithelium; however, weaker reaction was present in the endothelium in PBK cases. Minimal, but significantly elevated immunopositivity could be observed in the anterior and posterior stroma in the FECD group. Additionally, minimally, but significantly higher aggrecan immunoreaction was present in the anterior stroma in PBK and in the posterior stroma in both endothelial disorders. All three antibodies disclosed the strongest reaction in the posterior stroma either in PBK or in FECD cases. Conclusions: These extracellular matrix molecules disclosed up to moderate immunopositivity in the corneal layers in varying extents. Through their networking, bridging, and adhesive abilities these proteins are involved in corneal regeneration and tissue reorganization in endothelial dysfunction. LA - English DB - MTMT ER - TY - JOUR AU - Rupawala, Huzefa AU - Shah, Keshvi AU - Davies, Caitlin AU - Rose, Jamie AU - Colom-Cadena, Marti AU - Peng, Xianhui AU - Granat, Lucy AU - Aljuhani, Manal AU - Mizuno, Keiko AU - Troakes, Claire AU - Perez-Nievas, Beatriz Gomez AU - Morgan, Alan AU - So, Po-Wah AU - Hortobágyi, Tibor AU - Spires-Jones, Tara L AU - Noble, Wendy AU - Giese, Karl Peter TI - Cysteine string protein alpha accumulates with early pre-synaptic dysfunction in Alzheimer’s disease JF - BRAIN COMMUNICATIONS J2 - BRAIN COMMUN VL - 4 PY - 2022 IS - 4 PG - 15 SN - 2632-1297 DO - 10.1093/braincomms/fcac192 UR - https://m2.mtmt.hu/api/publication/33216546 ID - 33216546 AB - In Alzheimer’s disease, synapse loss causes memory and cognitive impairment. However, the mechanisms underlying synaptic degeneration in Alzheimer’s disease are not well understood. In the hippocampus, alterations in the level of cysteine string protein alpha, a molecular co-chaperone at the pre-synaptic terminal, occur prior to reductions in synaptophysin, suggesting that it is a very sensitive marker of synapse degeneration in Alzheimer’s. Here, we identify putative extracellular accumulations of cysteine string alpha protein, which are proximal to beta-amyloid deposits in post-mortem human Alzheimer’s brain and in the brain of a transgenic mouse model of Alzheimer’s disease. Cysteine string protein alpha, at least some of which is phosphorylated at serine 10, accumulates near the core of beta-amyloid deposits and does not co-localize with hyperphosphorylated tau, dystrophic neurites or glial cells. Using super-resolution microscopy and array tomography, cysteine string protein alpha was found to accumulate to a greater extent than other pre-synaptic proteins and at a comparatively great distance from the plaque core. This indicates that cysteine string protein alpha is most sensitive to being released from pre-synapses at low concentrations of beta-amyloid oligomers. Cysteine string protein alpha accumulations were also evident in other neurodegenerative diseases, including some fronto-temporal lobar dementias and Lewy body diseases, but only in the presence of amyloid plaques. Our findings are consistent with suggestions that pre-synapses are affected early in Alzheimer’s disease, and they demonstrate that cysteine string protein alpha is a more sensitive marker for early pre-synaptic dysfunction than traditional synaptic markers. We suggest that cysteine string protein alpha should be used as a pathological marker for early synaptic disruption caused by beta-amyloid. LA - English DB - MTMT ER - TY - JOUR AU - Gilvesy, Abris AU - Husen, Evelina AU - Maglóczky, Zsófia AU - Mihaly, Orsolya AU - Hortobágyi, Tibor AU - Kanatani, Shigeaki AU - Heinsen, Helmut AU - Renier, Nicolas AU - Hökfelt, Tomas AU - Mulder, Jan AU - Uhlen, Mathias AU - Kovacs, Gabor G. AU - Adori, Csaba TI - Spatiotemporal characterization of cellular tau pathology in the human locus coeruleus–pericoerulear complex by three-dimensional imaging JF - ACTA NEUROPATHOLOGICA J2 - ACTA NEUROPATHOL VL - 144 PY - 2022 IS - 4 SP - 651 EP - 676 PG - 26 SN - 0001-6322 DO - 10.1007/s00401-022-02477-6 UR - https://m2.mtmt.hu/api/publication/33091402 ID - 33091402 AB - Tau pathology of the noradrenergic locus coeruleus (LC) is a hallmark of several age-related neurodegenerative disorders, including Alzheimer’s disease. However, a comprehensive neuropathological examination of the LC is difficult due to its small size and rod-like shape. To investigate the LC cytoarchitecture and tau cytoskeletal pathology in relation to possible propagation patterns of disease-associated tau in an unprecedented large-scale three-dimensional view, we utilized volume immunostaining and optical clearing technology combined with light sheet fluorescence microscopy. We examined AT8 + pathological tau in the LC/pericoerulear region of 20 brains from Braak neurofibrillary tangle (NFT) stage 0–6. We demonstrate an intriguing morphological complexity and heterogeneity of AT8 + cellular structures in the LC, representing various intracellular stages of NFT maturation and their diverse transition forms. We describe novel morphologies of neuronal tau pathology such as AT8 + cells with fine filamentous somatic protrusions or with disintegrating soma. We show that gradual dendritic atrophy is the first morphological sign of the degeneration of tangle-bearing neurons, even preceding axonal lesions. Interestingly, irrespective of the Braak NFT stage, tau pathology is more advanced in the dorsal LC that preferentially projects to vulnerable forebrain regions in Alzheimer’s disease, like the hippocampus or neocortical areas, compared to the ventral LC projecting to the cerebellum and medulla. Moreover, already in the precortical Braak 0 stage, 3D analysis reveals clustering tendency and dendro-dendritic close appositions of AT8 + LC neurons, AT8 + long axons of NFT-bearing cells that join the ascending dorsal noradrenergic bundle after leaving the LC, as well as AT8 + processes of NFT-bearing LC neurons that target the 4th ventricle wall. Our study suggests that the unique cytoarchitecture, comprised of a densely packed and dendritically extensively interconnected neuronal network with long projections, makes the human LC to be an ideal anatomical template for early accumulation and trans-neuronal spreading of hyperphosphorylated tau. LA - English DB - MTMT ER - TY - JOUR AU - Zhong, Wen AU - Barde, Swapnali AU - Mitsios, Nicholas AU - Adori, Csaba AU - Oksvold, Per AU - Feilitzen, Kalle von AU - O’Leary, Liam AU - Csiba, László AU - Hortobágyi, Tibor AU - Szocsics, Péter AU - Mechawar, Naguib AU - Maglóczky, Zsófia AU - Dobolyiné Renner, Éva AU - Palkovits, Miklós AU - Uhlén, Mathias AU - Mulder, Jan AU - Hökfelt, Tomas TI - The neuropeptide landscape of human prefrontal cortex JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 119 PY - 2022 IS - 33 PG - 12 SN - 0027-8424 DO - 10.1073/pnas.2123146119 UR - https://m2.mtmt.hu/api/publication/33048618 ID - 33048618 N1 - D AB - Human prefrontal cortex (hPFC) is a complex brain region involved in cognitive and emotional processes and several psychiatric disorders. Here, we present an overview of the distribution of the peptidergic systems in 17 subregions of hPFC and three reference cortices obtained by microdissection and based on RNA sequencing and RNAscope methods integrated with published single-cell transcriptomics data. We detected expression of 60 neuropeptides and 60 neuropeptide receptors in at least one of the hPFC subregions. The results reveal that the peptidergic landscape in PFC consists of closely located and functionally different subregions with unique peptide/transmitter–related profiles. Neuropeptide-rich PFC subregions were identified, encompassing regions from anterior cingulate cortex/orbitofrontal gyrus. Furthermore, marked differences in gene expression exist between different PFC regions (>5-fold; cocaine and amphetamine–regulated transcript peptide) as well as between PFC regions and reference regions, for example, for somatostatin and several receptors. We suggest that the present approach allows definition of, still hypothetical, microcircuits exemplified by glutamatergic neurons expressing a peptide cotransmitter either as an agonist (hypocretin/orexin) or antagonist (galanin). Specific neuropeptide receptors have been identified as possible targets for neuronal afferents and, interestingly, peripheral blood-borne peptide hormones (leptin, adiponectin, gastric inhibitory peptide, glucagon-like peptides, and peptide YY). Together with other recent publications, our results support the view that neuropeptide systems may play an important role in hPFC and underpin the concept that neuropeptide signaling helps stabilize circuit connectivity and fine-tune/modulate PFC functions executed during health and disease. LA - English DB - MTMT ER - TY - JOUR AU - Sonkodi, Balázs AU - Resch, Miklós AU - Hortobágyi, Tibor TI - Is the Sex Difference a Clue to the Pathomechanism of Dry Eye Disease? Watch out for the NGF-TrkA-Piezo2 Signaling Axis and the Piezo2 Channelopathy JF - JOURNAL OF MOLECULAR NEUROSCIENCE J2 - J MOL NEUROSCI VL - 72 PY - 2022 IS - 8 SP - 1598 EP - 1608 PG - 11 SN - 0895-8696 DO - 10.1007/s12031-022-02015-9 UR - https://m2.mtmt.hu/api/publication/32806050 ID - 32806050 N1 - Received: 21 March 2022 / Accepted: 20 April 2022 Open access funding provided by University of Physical Education. LA - English DB - MTMT ER -