Strenzke, Nicola

[["dc.bibliographiccitation.firstpage","7587"],["dc.bibliographiccitation.issue","22"],["dc.bibliographiccitation.journal","The Journal of neuroscience"],["dc.bibliographiccitation.lastpage","7597"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Buran, Bradley N."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Neef, Andreas"],["dc.contributor.author","Gundelfinger, Eckart D."],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Liberman, M. Charles"],["dc.date.accessioned","2017-09-07T11:45:59Z"],["dc.date.available","2017-09-07T11:45:59Z"],["dc.date.issued","2010"],["dc.description.abstract","Synaptic ribbons, found at the presynaptic membrane of sensory cells in both ear and eye, have been implicated in the vesicle-pool dynamics of synaptic transmission. To elucidate ribbon function, we characterized the response properties of single auditory nerve fibers in mice lacking Bassoon, a scaffolding protein involved in anchoring ribbons to the membrane. In bassoon mutants, immunohistochemistry showed that fewer than 3% of the hair cells' afferent synapses retained anchored ribbons. Auditory nerve fibers from mutants had normal threshold, dynamic range, and postonset adaptation in response to tone bursts, and they were able to phase lock with normal precision to amplitude-modulated tones. However, spontaneous and sound-evoked discharge rates were reduced, and the reliability of spikes, particularly at stimulus onset, was significantly degraded as shown by an increased variance of first-spike latencies. Modeling based on in vitro studies of normal and mutant hair cells links these findings to reduced release rates at the synapse. The degradation of response reliability in these mutants suggests that the ribbon and/or Bassoon normally facilitate high rates of exocytosis and that its absence significantly compromises the temporal resolving power of the auditory system."],["dc.identifier.doi","10.1523/JNEUROSCI.0389-10.2010"],["dc.identifier.gro","3142908"],["dc.identifier.isi","000278288200016"],["dc.identifier.pmid","20519533"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/364"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Soc Neuroscience"],["dc.relation.issn","0270-6474"],["dc.title","Onset Coding Is Degraded in Auditory Nerve Fibers from Mutant Mice Lacking Synaptic Ribbons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Moore, Sharlen"],["dc.contributor.author","Meschkat, Martin"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Tzvetanova, Iva D."],["dc.contributor.author","Battefeld, Arne"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Kole, Maarten H. P."],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","de Hoz, Livia"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2021-04-14T08:31:48Z"],["dc.date.available","2021-04-14T08:31:48Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41467-020-19152-7"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83719"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2041-1723"],["dc.title","A role of oligodendrocytes in information processing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2005114"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Cruces-Solís, Hugo"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Babaev, Olga"],["dc.contributor.author","Rubin, Jonathan"],["dc.contributor.author","Gür, Burak"],["dc.contributor.author","Krueger-Burg, Dilja"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","de Hoz, Livia"],["dc.date.accessioned","2020-11-24T10:40:59Z"],["dc.date.available","2020-11-24T10:40:59Z"],["dc.date.issued","2018"],["dc.description.abstract","Detecting regular patterns in the environment, a process known as statistical learning, is essential for survival. Neuronal adaptation is a key mechanism in the detection of patterns that are continuously repeated across short (seconds to minutes) temporal windows. Here, we found in mice that a subcortical structure in the auditory midbrain was sensitive to patterns that were repeated discontinuously, in a temporally sparse manner, across windows of minutes to hours. Using a combination of behavioral, electrophysiological, and molecular approaches, we found changes in neuronal response gain that varied in mechanism with the degree of sound predictability and resulted in changes in frequency coding. Analysis of population activity (structural tuning) revealed an increase in frequency classification accuracy in the context of increased overlap in responses across frequencies. The increase in accuracy and overlap was paralleled at the behavioral level in an increase in generalization in the absence of diminished discrimination. Gain modulation was accompanied by changes in gene and protein expression, indicative of long-term plasticity. Physiological changes were largely independent of corticofugal feedback, and no changes were seen in upstream cochlear nucleus responses, suggesting a key role of the auditory midbrain in sensory gating. Subsequent behavior demonstrated learning of predictable and random patterns and their importance in auditory conditioning. Using longer timescales than previously explored, the combined data show that the auditory midbrain codes statistical learning of temporally sparse patterns, a process that is critical for the detection of relevant stimuli in the constant soundscape that the animal navigates through."],["dc.identifier.doi","10.1371/journal.pbio.2005114"],["dc.identifier.pmid","30048446"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15664"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69155"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1545-7885"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Auditory midbrain coding of statistical learning that results from discontinuous sensory stimulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","673"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neuroscience"],["dc.bibliographiccitation.lastpage","684"],["dc.bibliographiccitation.volume","149"],["dc.contributor.author","Pauli-Magnus, D."],["dc.contributor.author","Hoch, G."],["dc.contributor.author","Strenzke, N."],["dc.contributor.author","Anderson, S."],["dc.contributor.author","Jentsch, T. J."],["dc.contributor.author","Moser, T."],["dc.date.accessioned","2017-09-07T11:49:23Z"],["dc.date.available","2017-09-07T11:49:23Z"],["dc.date.issued","2007"],["dc.description.abstract","Sensorineural hearing loss (SNHL) comprises hearing disorders with diverse pathologies of the inner ear and the auditory nerve. To date, an unambiguous phenotypical characterization of the specific pathologies in an affected individual remains impossible. Here, we evaluated the use of scalp-recorded auditory steady-state responses (ASSR) and transient auditory brainstem responses (ABR) for differentiating the disease mechanisms underlying sensorineural hearing loss in well-characterized mouse models. We first characterized the ASSR evoked by sinusoidally amplitude-modulated tones in wild-type mice. ASSR were robustly elicited within three ranges of modulation frequencies below 200 Hz, from 200 to 600 Hz and beyond 600 Hz in most recordings. Using phase information we estimated the apparent ASSR latency to be about 3 ms, suggesting generation in the auditory brainstem. Auditory thresholds obtained by automated and visual analysis of ASSR recordings were comparable to those found with tone-burst evoked ABR in the same mice. We then recorded ASSR and ABR from mouse mutants bearing defects of either outer hair cell amplification (KC NQ4- knockout) or inner hair cell synaptic transmission (Bassoon-mutant). Both mutants showed an increase of ASSR and ABR thresholds of approximately 40 dB versus wild-type when investigated at 8 weeks of age. Mice with defective amplification displayed a steep rise of ASSR and ABR amplitudes with increasing sound intensity, presumably reflecting a strong recruitment of synchronously activated neural elements beyond threshold. In contrast, the amplitudes of ASSR and ABR responses of mice with impaired synaptic transmission grew very little with sound intensity. In summary, ASSR allow for a rapid, objective and frequency-specific hearing assessment and together with ABR and otoacoustic emissions can contribute to the differential diagnosis of SNHL. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.neuroscience.2007.08.010"],["dc.identifier.gro","3143413"],["dc.identifier.isi","000251022900020"],["dc.identifier.pmid","17869440"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/925"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0306-4522"],["dc.title","Detection and differentiation of sensorineural hearing loss in mice using auditory steady-state responses and transient auditory brainstem responses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e52069"],["dc.bibliographiccitation.issue","92"],["dc.bibliographiccitation.journal","Journal of Visualized Experiments"],["dc.contributor.author","Hernandez, Victor H."],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Jing, Zhizi"],["dc.contributor.author","Hoch, Gerhard"],["dc.contributor.author","Jeschke, Marcus"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2017-09-07T11:45:27Z"],["dc.date.available","2017-09-07T11:45:27Z"],["dc.date.issued","2014"],["dc.description.abstract","Direct electrical stimulation of spiral ganglion neurons (SGNs) by cochlear implants (CIs) enables open speech comprehension in the majority of implanted deaf subjects(1-6). Nonetheless, sound coding with current CIs has poor frequency and intensity resolution due to broad current spread from each electrode contact activating a large number of SGNs along the tonotopic axis of the cochlea(7-9). Optical stimulation is proposed as an alternative to electrical stimulation that promises spatially more confined activation of SGNs and, hence, higher frequency resolution of coding. In recent years, direct infrared illumination of the cochlea has been used to evoke responses in the auditory nerve(10). Nevertheless it requires higher energies than electrical stimulation(10,11) and uncertainty remains as to the underlying mechanism(12). Here we describe a method based on optogenetics to stimulate SGNs with low intensity blue light, using transgenic mice with neuronal expression of channelrhodopsin 2 (ChR2)(13) or virus-mediated expression of the ChR2-variant CatCh(14). We used micro-light emitting diodes (mu LEDs) and fiber-coupled lasers to stimulate ChR2-expressing SGNs through a small artificial opening (cochleostomy) or the round window. We assayed the responses by scalp recordings of light-evoked potentials (optogenetic auditory brainstem response: oABR) or by microelectrode recordings from the auditory pathway and compared them with acoustic and electrical stimulation."],["dc.identifier.doi","10.3791/52069"],["dc.identifier.gro","3142038"],["dc.identifier.isi","000349303100063"],["dc.identifier.pmid","25350571"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3856"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1940-087X"],["dc.title","Optogenetic Stimulation of the Auditory Nerve. Towards an Optical Cochlear Prosthetic"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2926"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","2931"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Schmitz, F."],["dc.contributor.author","Tabares, Lucia"],["dc.contributor.author","Khimich, Darina"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Villa-Polo, P. de la"],["dc.contributor.author","Castellano-Munoz, M."],["dc.contributor.author","Bulankina, Anna V."],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Fernandez-Chacon, R"],["dc.contributor.author","Suedhof, Thomas C."],["dc.date.accessioned","2017-09-07T11:53:17Z"],["dc.date.available","2017-09-07T11:53:17Z"],["dc.date.issued","2006"],["dc.description.abstract","Cysteine string protein (CSP) alpha is an abundant synaptic vesicle protein that contains a DNA-J domain characteristic of Hsp40-type cochaperones. Previous studies showed that deletion of CSP alpha in mice leads to massive lethal neurodegeneration but did not clarify how the neurodegeneration affects specific subpopulations of neurons. Here, we analyzed the effects of the CSP alpha deficiency on tonically active ribbon synapses of the retina and the inner ear. We show that CSP alpha-deficient photoreceptor terminals undergo dramatic and rapidly progressive neurodegeneration that starts before eye opening and initially does not affect other retinal synapses. These changes are associated with progressive blindness. In contrast, ribbon synapses of auditory hair cells did not exhibit presynaptic impairments in CSP alpha-deficient mice. Hair cells, but not photoreceptor cells or central neurons, express CSP beta, thereby accounting for the lack of a hair-cell phenotype in CSP alpha knockout mice. Our data demonstrate that tonically active ribbon synapses in retina are particularly sensitive to the deletion of CSP alpha and that expression of at least one CSP isoform is essential to protect such tonically active synapses from neurodegeneration."],["dc.identifier.doi","10.1073/pnas.0510060103"],["dc.identifier.gro","3143736"],["dc.identifier.isi","000235554900080"],["dc.identifier.pmid","16477021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1283"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","CSP alpha-deficiency causes massive and rapid photoreceptor degeneration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","28"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","39"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Schuetz, Melanie"],["dc.contributor.author","Auth, Tanja"],["dc.contributor.author","Gehrt, Anna"],["dc.contributor.author","Bosen, Felicitas"],["dc.contributor.author","Koerber, Inken"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Willecke, Klaus"],["dc.date.accessioned","2017-09-07T11:45:05Z"],["dc.date.available","2017-09-07T11:45:05Z"],["dc.date.issued","2011"],["dc.description.abstract","Mutations in the GJB2 gene coding for connexin26 (Cx26) can cause a variety of deafness and hereditary hyperproliferative skin disorders in humans. In this study, we investigated the Cx26S17F mutation in mice, which had been identified to cause the keratitis-ichthyosis-deafness (KID) syndrome in humans. The KID syndrome is characterized by keratitis and chronic progressive corneal neovascularization, skin hyperplasia, sensorineural hearing loss and increased carcinogenic potential. We have generated a conditional mouse mutant, in which the floxed wild-type Cx26-coding DNA can be deleted and the Cx26S17F mutation is expressed under control of the endogenous Cx26 promoter. Homozygous mutants are not viable, whereas the surviving heterozygous mice show hyperplasia of tail and foot epidermis, wounded tails and annular tail restrictions, and are smaller than their wild-type littermates. Analyses of auditory brainstem responses (ABRs) indicate an similar to 35 dB increased hearing threshold in these mice, which is likely due to the reduction of the endocochlear potential by 20-40%. Our results indicate that the Cx26S17F protein, which does not form functional gap junction channels or hemichannels, alters epidermal proliferation and differentiation in the heterozygous state. In the inner ear, reduced intercellular coupling by heteromeric channels composed of Cx26S17F and Cx30 could contribute to hearing impairment in heterozygous mice, while remaining wild-type Cx26 may be sufficient to stabilize Cx30 and partially maintain cochlear homeostasis. The phenotype of heterozygous mice resembles many of the symptoms of the human KID syndrome. Thus, these mice represent an appropriate model to further investigate the disease mechanism."],["dc.identifier.doi","10.1093/hmg/ddq429"],["dc.identifier.gro","3142801"],["dc.identifier.isi","000285193600003"],["dc.identifier.pmid","20926451"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/245"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.eissn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","The connexin26 S17F mouse mutant represents a model for the human hereditary keratitis-ichthyosis-deafness syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","531"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Laryngoscope"],["dc.bibliographiccitation.lastpage","537"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Ihler, Friedrich"],["dc.contributor.author","Koehler, Sabrina"],["dc.contributor.author","Meyer, Alexander C."],["dc.contributor.author","Blum, Jenny"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Matthias, Christoph"],["dc.contributor.author","Canis, Martin"],["dc.date.accessioned","2018-11-07T09:44:44Z"],["dc.date.available","2018-11-07T09:44:44Z"],["dc.date.issued","2014"],["dc.description.abstract","Objectives/HypothesisTo review the results of obliteration of a preexisting mastoid cavity with abdominal fat and Vibrant Soundbridge implantation in patients with mixed hearing loss (MHL) and to compare the data with results of Vibrant Soundbridge implantation in patients with MHL without mastoid cavity and with pure sensorineural hearing loss (SNHL). Study DesignRetrospective chart analysis of 10 patients (10 ears) with MHL and preexisting mastoid cavity, 18 patients (19 ears) with MHL alone and nine patients (10 ears) with SNHL treated in one tertiary referral center. MethodsVibrant Soundbridge implantation and obliteration in case a mastoid cavity existed previously. Pure tone audiometry (average air-bone gap, average functional gain), speech audiometry (Freiburg Monosyllabic Test) and complication rate were main outcome measures. ResultsPostoperative average air-bone gap was -15.121.2 dB in patients with MHL with mastoid cavity obliteration, -7.211.4 dB in patients with MHL without mastoid cavity, and -5.7 +/- 11.2 dB in patients with SNHL. Average functional gain was 40.0 +/- 23.5 dB, 39.7 +/- 12.1 dB, and 9.5 +/- 10.6 dB. Postoperative speech discrimination rate was 77.9 +/- 20.8%, 83.3 +/- 13.6%, and 83.6 +/- 6.3%. No severe intraoperative or postoperative complications were noted. ConclusionsMastoid cavity obliteration during Vibrant Soundbridge implantation in patients with MHL and preexisting mastoid cavity is a safe procedure. The audiometric results are satisfying and comparable to those of other patient groups implanted with the same device. Level of Evidence4. Laryngoscope, 124:531-537, 2014"],["dc.description.sponsorship","MED-EL, Innsbruck, Austria"],["dc.identifier.doi","10.1002/lary.24180"],["dc.identifier.isi","000329929900041"],["dc.identifier.pmid","23918587"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34461"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1531-4995"],["dc.relation.issn","0023-852X"],["dc.title","Mastoid Cavity Obliteration and Vibrant Soundbridge Implantation for Patients With Mixed Hearing Loss"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Rankovic, Vladan"],["dc.contributor.author","Vogl, Christian"],["dc.contributor.author","Dörje, Nele M."],["dc.contributor.author","Bahader, Iman"],["dc.contributor.author","Duque-Afonso, Carlos J."],["dc.contributor.author","Thirumalai, Anupriya"],["dc.contributor.author","Weber, Thomas"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Moser, Tobias"],["dc.date.accessioned","2021-04-14T08:29:50Z"],["dc.date.available","2021-04-14T08:29:50Z"],["dc.date.issued","2021"],["dc.description.abstract","Hearing impairment is the most common sensory disorder in humans. So far, rehabilitation of profoundly deaf subjects relies on direct stimulation of the auditory nerve through cochlear implants. However, in some forms of genetic hearing impairment, the organ of Corti is structurally intact and therapeutic replacement of the mutated gene could potentially restore near natural hearing. In the case of defects of the otoferlin gene (OTOF), such gene therapy is hindered by the size of the coding sequence (~6 kb) exceeding the cargo capacity (\\u0026lt;5 kb) of the preferred viral vector, adeno-associated virus (AAV). Recently, a dual-AAV approach was used to partially restore hearing in deaf otoferlin knock-out (Otof-KO) mice. Here, we employed in vitro and in vivo approaches to assess the gene-therapeutic potential of naturally-occurring and newly-developed synthetic AAVs overloaded with the full-length Otof coding sequence. Upon early postnatal injection into the cochlea of Otof-KO mice, overloaded AAVs drove specific expression of otoferlin in ~30% of all IHCs, as demonstrated by immunofluorescence labeling and polymerase chain reaction. Recordings of auditory brainstem responses and a behavioral assay demonstrated partial restoration of hearing. Together, our results suggest that viral gene therapy of DFNB9—using a single overloaded AAV vector—is indeed feasible, reducing the complexity of gene transfer compared to dual-AAV approaches."],["dc.identifier.doi","10.3389/fnmol.2020.600051"],["dc.identifier.pmid","33488357"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83002"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/123"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","Frontiers Media S.A."],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1662-5099"],["dc.relation.workinggroup","RG Moser (Molecular Anatomy, Physiology and Pathology of Sound Encoding)"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Overloaded Adeno-Associated Virus as a Novel Gene Therapeutic Tool for Otoferlin-Related Deafness"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","567"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","586"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Kraemer-Albers, Eva-Maria"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Tenzer, Stefan"],["dc.contributor.author","Ohno-Iwashita, Yoshiko"],["dc.contributor.author","Monasterio-Schrader, Patricia de"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Griffiths, Ian R."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2017-09-07T11:47:44Z"],["dc.date.available","2017-09-07T11:47:44Z"],["dc.date.issued","2013"],["dc.description.abstract","The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that high cholesterol is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport. (c) 2013 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/glia.22456"],["dc.identifier.gro","3142368"],["dc.identifier.isi","000314981400010"],["dc.identifier.pmid","23322581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7508"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: BMBF; European Commission"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.title","A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]