Herken, Rainer

[["dc.bibliographiccitation.journal","Glia"],["dc.contributor.author","Nico, B."],["dc.contributor.author","Corsi, P."],["dc.contributor.author","Frigeri, A."],["dc.contributor.author","Nicchia, G. P."],["dc.contributor.author","Mangieri, D."],["dc.contributor.author","Frontino, A."],["dc.contributor.author","Quondamatteo, Fabio"],["dc.contributor.author","Herken, R."],["dc.contributor.author","Ribatti, D."],["dc.contributor.author","Svelto, M."],["dc.contributor.author","Roncali, L."],["dc.date.accessioned","2018-11-07T10:36:31Z"],["dc.date.available","2018-11-07T10:36:31Z"],["dc.date.issued","2003"],["dc.format.extent","29"],["dc.identifier.isi","000184938300123"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45347"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.publisher.place","New york"],["dc.relation.conference","6th European Meeting on Glial Cell Function in Health and Disease"],["dc.relation.eventlocation","BERLIN, GERMANY"],["dc.relation.issn","0894-1491"],["dc.title","Blood-brain barrier alterations in dystrophic mdx mice"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1297"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Journal of Cell Science"],["dc.bibliographiccitation.lastpage","1307"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Nico, B."],["dc.contributor.author","Frigeri, A."],["dc.contributor.author","Nicchia, G. P."],["dc.contributor.author","Quondamatteo, Fabio"],["dc.contributor.author","Herken, R."],["dc.contributor.author","Errede, M."],["dc.contributor.author","Ribatti, D."],["dc.contributor.author","Svelto, M."],["dc.contributor.author","Roncali, L."],["dc.date.accessioned","2018-11-07T09:12:56Z"],["dc.date.available","2018-11-07T09:12:56Z"],["dc.date.issued","2001"],["dc.description.abstract","In this study, we have investigated the expression of aquaporin 4 during blood-brain barrier development in the optic tectum of chick embryos and newly hatched chicks, by means of western-blot! reverse transcriptase-polymerase chain reaction, immunohistochemistry, and freeze-fracture and high-resolution immunogold electron microscopy In the optic tecta of day-14 embryos, western blot analysis revealed an approx, 30 kDa band, immunoreactive for aquaporin-4, which was increased in day-20 embryos and in chicks, Semi-quantitative reverse transcriptase chain reaction experiments showed that there was already a high level of aquaporin-4 mRNA in day-9 embryos as well as in the subsequent stages and in newly hatched chicks, Immunohistochemically, reactivity for aquaporin-4 was detected in the optic tectum of day-14 embryos; similar results were obtained in telencephalon and cerebellum, Ultrastructurally; the microvessels of the tectum showed immunoreactivity. for aquaporin-4 on the astroglial endfeet, which discontinuously surrounded endothelial cells joined hy immature tight junctions, In the tectum, telencephalon and cerebellum of 20-day embryos and chicks, aquaporin-4 strongly labeled the ependymal cells and the subpial glial membranes, as well as the bodies and processes of astroglial cells. A continuous aquaporin-4 staining was found around the microvessel endothelial cells, which were sealed off from one another by extensive tight junctions, A complete astrocytic sheath, labeled hg anti-aquaporin-4 gold particles, enveloped the endothelial-pericyte layer. Orthogonal arrays of particles were observed on fractured astrocytic membranes, starting from embryonic day 14 when the aquaporin-4 immunogold staining revealed clusters of gold particles, often forming square or rectangular clusters, The results showed that aquaporin-4 expression and organization of the intramembrane particles in orthogonal arrays followed the same temporal sequence, Finally, the lipopolysaccharide, a substance that induces blood-brain barrier distruption, determines a remarkable reduction in aquaporin-4 labeling, expressed by a few aquaporin-4 gold particles attached on swollen perivascular glial membranes, All these data show that aquaporin-4 expression occurs in the chick embryonic brain, in parallel with maturation and functioning of the blood-brain barrier and suggest that there is a close relationship between water transport regulation and brain development."],["dc.description.sponsorship","Telethon [983]"],["dc.identifier.isi","000168205200007"],["dc.identifier.pmid","11256996"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27058"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Company Of Biologists Ltd"],["dc.relation.issn","0021-9533"],["dc.title","Role of aquaporin-4 water channel in the development and integrity of the blood-brain barrier"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","90"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.lastpage","98"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Frigeri, A."],["dc.contributor.author","Nicchia, G. P."],["dc.contributor.author","Nico, B."],["dc.contributor.author","Quondamatteo, Fabio"],["dc.contributor.author","Herken, R."],["dc.contributor.author","Roncali, L."],["dc.contributor.author","Svelto, M."],["dc.date.accessioned","2018-11-07T09:32:44Z"],["dc.date.available","2018-11-07T09:32:44Z"],["dc.date.issued","2001"],["dc.description.abstract","We report a detailed study of AQP4 expression in the neuromuscular system of mdx mice. Immunocytochemical analysis performed by double immunostaining revealed that mdx mice manifest a progressive reduction in AQP4 at the sarcolemmal level of skeletal muscle fast fibers and that type IIB fibers are the first to manifest this reduction in AQP4 expression. No labeling was observed in the cytoplasm of muscle fibers, indicating that the reduction in sarcolemma staining is not associated with an intracellular compartmentalization of mistargeted protein. By Western blot and RT-PCR analysis, we found that whereas the total content of AQP4 protein decreased (by 90% in adult mdx mice), mRNA levels for AQP4 remained unchanged. A similar age-related reduction in AQP4 expression was found in brain astrocytic end-feet surrounding capillaries of mdx mice. Morphometric analysis performed after immunogold electron microscopy indicated a reduction of similar to 85% in gold particles (32 +/-2/mum vs. 4.7 +/-0.61/mum). Western blot experiments conducted using membrane fractions from brain cortex revealed a strong reduction (of 70%) in AQP4 protein in adult mdx mice, and RT-PCR experiments demonstrated that the reduction was not at transcription level. More interesting was the finding that AQP4 reduction was associated with swelling of astrocytic perivascular processes whose ultrastructural modifications are commonly indicated as an important and early event in the development of brain edema. No apparent reduction in AQP4 was found in mdx stomach and kidney. Our data provide evidence that dystrophin deficiency in mdx mice leads to disturbances in AQP4 assembly in the plasma membrane of fast skeletal muscle fibers and brain astrocytic end-feet, suggesting that changes in the osmotic equilibrium of the neuromuscular apparatus may be involved in the pathology of muscular dystrophy."],["dc.description.sponsorship","Telethon [983]"],["dc.identifier.doi","10.1096/fj.00-0260com"],["dc.identifier.isi","000166312400017"],["dc.identifier.pmid","11149896"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31811"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","0892-6638"],["dc.title","Aquaporin-4 deficiency in skeletal muscle and brain of dystrophic mdx mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","231"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","DEVELOPMENTAL BRAIN RESEARCH"],["dc.bibliographiccitation.lastpage","242"],["dc.bibliographiccitation.volume","119"],["dc.contributor.author","Nico, B."],["dc.contributor.author","Quondamatteo, Fabio"],["dc.contributor.author","Herken, R."],["dc.contributor.author","Blumchen, T."],["dc.contributor.author","Defazio, G."],["dc.contributor.author","Giorelli, M."],["dc.contributor.author","Livrea, P."],["dc.contributor.author","Marzullo, A."],["dc.contributor.author","Russo, G."],["dc.contributor.author","Ribatti, D."],["dc.contributor.author","Roncali, L."],["dc.date.accessioned","2018-11-07T10:03:04Z"],["dc.date.available","2018-11-07T10:03:04Z"],["dc.date.issued","2000"],["dc.description.abstract","By means of light and electron microscopy we have studied the effect of interferon beta-1a (IFN beta-1a) in the optic tecta of 20-day-old chick embryos under normal conditions and after exposure to lipopolysaccharide (LPS) which mimics the blood-brain barrier (BBB) disruption in meningoencephalitis. Optic tecta were examined for: (i) ultrastructure by means of transmission electron microscopy; (ii) the immunohistochemical localization of HT7 antigen, a specific marker of differentiation of the brain microvessels; (iii) the brain microvessel permeability, by means of horseradish peroxidase (HRP) tracer; (iv) the expression of microvessel glycoconjugates, by means of lectin histochemistry, using Ricinus communis agglutinin-1 (RCA-I), specific for beta-D-galactosyl moieties and Wheat Germ agglutinin (WGA) specific for sialyl and N-acetylglucosaminyl moieties. A morphometric evaluation of brain microvessel permeability and of glycoconjugate expression was also performed. In control- and in IFN beta-1a-treated embryos, HRP was confined to the vessel lumina which were sealed by the interendothelial tight junctions. RCA-I binding sites were recognizable both in the basal membranes and in the tight junctions, while WGA sites were present on the luminal side of the endothelial cells. HRP was blocked in the vessels lumina by the interendothelial tight junctions. After LPS treatment, HRP showed an extravascular localization and the labeling of microvessels by anti-HT7 antibodies disappeared. RCA-I binding was only found ultrastructurally and appeared as irregularly clustered gold particles, in the cleft of damaged tight junctions, but were no longer detectable in the endothelial basement membranes. After pretreatment of LPS-treated embryos with IFN beta-1a, the vessel permeability to HRP strongly decreased and the vessels showed the normal pattern of HT7 protein and of the RCA-I binding sites. These results indicate that the changes induced by LPS in the endothelial cells are prevented by IFN beta-1a. (C) 2000 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0165-3806(99)00177-7"],["dc.identifier.isi","000085355100009"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38367"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0165-3806"],["dc.title","Interferon beta-1a prevents the effects of lipopolysaccharide on embryonic brain microvessels"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","235"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","251"],["dc.bibliographiccitation.volume","42"],["dc.contributor.author","Nico, B."],["dc.contributor.author","Frigeri, A."],["dc.contributor.author","Nicchia, G. P."],["dc.contributor.author","Corsi, P."],["dc.contributor.author","Ribatti, D."],["dc.contributor.author","Quondamatteo, Fabio"],["dc.contributor.author","Herken, R."],["dc.contributor.author","Girolamo, F."],["dc.contributor.author","Marzullo, A."],["dc.contributor.author","Svelto, M."],["dc.contributor.author","Roncali, L."],["dc.date.accessioned","2018-11-07T10:39:11Z"],["dc.date.available","2018-11-07T10:39:11Z"],["dc.date.issued","2003"],["dc.description.abstract","In this study, we investigated the involvement of the blood-brain barrier (BBB) in the brain of the dystrophin-deficient mdx mouse, an experimental model of Duchenne muscular dystrophy (DMD). To this purpose, we used two tight junction markers, the Zonula occludens (ZO-1) and claudin-1 proteins, and a glial marker, the aquaporin-4 (AQP4) protein, whose expression is correlated with BBB differentiation and integrity. Results showed that most of the brain microvessels in mdx mice were lined by altered endothelial cells that showed open tight junctions and were surrounded by swollen glial processes. Moreover, 18% of the perivascular glial endfeet contained electron-dense cellular debris and were enveloped by degenerating microvessels. Western blot showed a 60% reduction in the ZO-1 protein content in mdx mice and a similar reduction in AQP4 content compared with the control brain. ZO-1 immunocytochemistry and claudin-1 immunofluorescence in mdx mice revealed a diffuse staining of microvessels as compared with the control ones, which displayed a banded staining pattern. ZO-1 immunogold electron microscopy showed unlabeled tight junctions and the presence of gold particles scattered in the endothelial cytoplasm in the mdx mice, whereas ZO-1 gold particles were exclusively located at the endothelial tight junctions in the controls. Dual immunofluorescence staining of a-actin and ZO-1 revealed colocalization of these proteins. As in ZO-1 staining, the pattern of immunolabeling with anti-alpha-actin antibody was diffuse in the mdx vessels and pointed or banded in the controls. a-actin immunogold electron microscopy showed gold particles in the cytoplasms of endothelial cells and pericytes in the mdx mice, whereas alpha-actin gold particles were revealed on the endothelial tight junctions and the cytoskeletal microfilaments of pericytes in the controls. Perivascular glial processes of the mdx mice appeared faintly stained by anti-AQP4 antibody, while in the controls a strong AQP4 labeling of glial processes was detected at light and electron microscope level. The vascular permeability of the mdx brain microvessels was investigated by means of the horseradish peroxidase (HRP). After HRP injection, extensive perivascular areas of marker escape were observed in mdx mice, whereas HRP was exclusively intravascularly localized in the controls. Inflammatory cells, CD4-, CD8-, CD20-, and CD68-positive cells, were not revealed in the perivascular stroma of the mdx brain. These findings indicate that dystrophin deficiency in the mdx brain leads to severe injury of the endothelial and glial cells with disturbance in alpha-actin cytoskeleton, ZO-1, claudin-1, and AQP4 assembly, as well as BBB breakdown. The BBB alterations suggest that changes in vascular permeability are involved in the pathogenesis of the neurological dysfunction associated with DMD."],["dc.identifier.doi","10.1002/glia.10216"],["dc.identifier.isi","000182480700003"],["dc.identifier.pmid","12673830"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45986"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0894-1491"],["dc.title","Severe alterations of endothelial and glial cells in the blood-brain barrier of dystrophic mdx mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","29"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","38"],["dc.bibliographiccitation.volume","31"],["dc.contributor.author","Nicchia, G. P."],["dc.contributor.author","Frigeri, A."],["dc.contributor.author","Liuzzi, G. M."],["dc.contributor.author","Santacroce, M. P."],["dc.contributor.author","Nico, B."],["dc.contributor.author","Procino, G."],["dc.contributor.author","Quondamatteo, Fabio"],["dc.contributor.author","Herken, R."],["dc.contributor.author","Roncali, L."],["dc.contributor.author","Svelto, M."],["dc.date.accessioned","2018-11-07T10:41:09Z"],["dc.date.available","2018-11-07T10:41:09Z"],["dc.date.issued","2000"],["dc.description.abstract","In order to understand the molecular mechanism underlying astroglial swelling, we studied primary astrocyte cultures from newborn mouse and analyzed them for expression of functional water channels. Immunocytochemical analysis of mouse brain confirms the presence of AQP4 location in astrocytic endfeet with a polarized pattern, as found in rat. Using Southern blot PCR and Western blot analysis, we demonstrate that primary astrocyte cultures from mouse express the AQP4 water channel at both the RNA and protein levels. Two polypeptides, of 30 kDa and 32 kDa, were identified in the astrocytes. Densitometric analysis demonstrates that the 32-kDa form represents 25% of the total AQP4 protein. Moreover, immunofluorescence experiments show strong surface membrane expression of AQP4 protein in cultured cells, even though the polarity of the expression is not maintained. Furthermore, functional studies indicate that cultured astrocytes manifest rapid and temperature-independent volume changes in response to osmotic gradients, in agreement with a channel-mediated water transport. Water movement was found to be HgCl2 insensitive, suggesting AQP4 and AQP7 as putative water channels. Using Western blot and PCR experiments, we exclude the presence of AQP7 in astrocytes, indicating that only AQP4 is responsible for the rapid water movement. Altogether, the results indicate that primary astrocyte cultures are a valid cell model for further investigation of the molecular mechanism of water movement in the brain and its physiological regulation. (C) 2000 Wiley-Liss, Inc."],["dc.description.sponsorship","Telethon [983]"],["dc.identifier.doi","10.1002/(SICI)1098-1136(200007)31:1<29::AID-GLIA30>3.0.CO;2-3"],["dc.identifier.isi","000087654600003"],["dc.identifier.pmid","10816604"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46470"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.relation.issn","0894-1491"],["dc.title","Aquaporin-4-containing astrocytes sustain a temperature- and mercury-insensitive swelling in vitro"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]