Hirrlinger, Johannes

[["dc.bibliographiccitation.firstpage","e3000943"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Steyer, Anna M."],["dc.contributor.author","Gregor, Ingo"],["dc.contributor.author","Nardis, Christos"],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Köhler, Susanne"],["dc.contributor.author","Restrepo, Alejandro"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.date.accessioned","2021-04-14T08:31:16Z"],["dc.date.available","2021-04-14T08:31:16Z"],["dc.date.issued","2020"],["dc.description.abstract","In several neurodegenerative disorders, axonal pathology may originate from impaired oligodendrocyte-to-axon support of energy substrates. We previously established transgenic mice that allow measuring axonal ATP levels in electrically active optic nerves. Here, we utilize this technique to explore axonal ATP dynamics in the Plpnull/y mouse model of spastic paraplegia. Optic nerves from Plpnull/y mice exhibited lower and more variable basal axonal ATP levels and reduced compound action potential (CAP) amplitudes, providing a missing link between axonal pathology and a role of oligodendrocytes in brain energy metabolism. Surprisingly, when Plpnull/y optic nerves are challenged with transient glucose deprivation, both ATP levels and CAP decline slower, but recover faster upon reperfusion of glucose. Structurally, myelin sheaths display an increased frequency of cytosolic channels comprising glucose and monocarboxylate transporters, possibly facilitating accessibility of energy substrates to the axon. These data imply that complex metabolic alterations of the axon–myelin unit contribute to the phenotype of Plpnull/y mice."],["dc.identifier.doi","10.1371/journal.pbio.3000943"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83539"],["dc.identifier.url","https://for2848.gwdguser.de/literature/publications/20"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","FOR 2848: Architektur und Heterogenität der inneren mitochondrialen Membran auf der Nanoskala"],["dc.relation","FOR 2848 | P08: Strukturelle und funktionale Veränderungen der inneren mitochondrialen Membran axonaler Mitochondrien in vivo in einem dymyelinisierenden Mausmodell"],["dc.relation.eissn","1545-7885"],["dc.relation.workinggroup","RG Möbius"],["dc.rights","CC BY 4.0"],["dc.title","Structural myelin defects are associated with low axonal ATP levels but rapid recovery from energy deprivation in a mouse model of spastic paraplegia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0129934"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Besser, Stefanie"],["dc.contributor.author","Sicker, Marit"],["dc.contributor.author","Marx, Grit"],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Eulenburg, Volker"],["dc.contributor.author","Huelsmann, Swen"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.date.accessioned","2018-11-07T09:55:52Z"],["dc.date.available","2018-11-07T09:55:52Z"],["dc.date.issued","2015"],["dc.description.abstract","GABAergic inhibitory neurons are a large population of neurons in the central nervous system (CNS) of mammals and crucially contribute to the function of the circuitry of the brain. To identify specific cell types and investigate their functions labelling of cell populations by transgenic expression of fluorescent proteins is a powerful approach. While a number of mouse lines expressing the green fluorescent protein (GFP) in different subpopulations of GABAergic cells are available, GFP expressing mouse lines are not suitable for either crossbreeding to other mouse lines expressing GFP in other cell types or for Ca2+-imaging using the superior green Ca2+-indicator dyes. Therefore, we have generated a novel transgenic mouse line expressing the red fluorescent protein tdTomato in GABAergic neurons using a bacterial artificial chromosome based strategy and inserting the tdTomato open reading frame at the start codon within exon 1 of the GAD2 gene encoding glutamic acid decarboxylase 65 (GAD65). TdTomato expression was observed in all expected brain regions; however, the fluorescence intensity was highest in the olfactory bulb and the striatum. Robust expression was also observed in cortical and hippocampal neurons, Purkinje cells in the cerebellum, amacrine cells in the retina as well as in cells migrating along the rostral migratory stream. In cortex, hippocampus, olfactory bulb and brainstem, 80% to 90% of neurons expressing endogenous GAD65 also expressed the fluorescent protein. Moreover, almost all tdTomato-expressing cells coexpressed GAD65, indicating that indeed only GABAergic neurons are labelled by tdTomato expression. This mouse line with its unique spectral properties for labelling GABAergic neurons will therefore be a valuable new tool for research addressing this fascinating cell type."],["dc.description.sponsorship","\"Deutsche Forschungsgemeinschaft\" (DFG) [HI1414/2-1, HU797/7-1]"],["dc.identifier.doi","10.1371/journal.pone.0129934"],["dc.identifier.isi","000356329900114"],["dc.identifier.pmid","26076353"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11956"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36843"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A Transgenic Mouse Line Expressing the Red Fluorescent Protein tdTomato in GABAergic Neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Cellular Neuroscience"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.contributor.author","Marx, Grit"],["dc.contributor.author","Besser, Stefanie"],["dc.contributor.author","Sicker, Marit"],["dc.contributor.author","Köhler, Susanne"],["dc.contributor.author","Hirrlinger, Petra G."],["dc.contributor.author","Wojcik, Sonja M."],["dc.contributor.author","Eulenburg, Volker"],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Hülsmann, Swen"],["dc.date.accessioned","2020-12-10T18:44:31Z"],["dc.date.available","2020-12-10T18:44:31Z"],["dc.date.issued","2019"],["dc.description.abstract","Inhibitory neurons crucially contribute to shaping the breathing rhythm in the brain stem. These neurons use GABA or glycine as neurotransmitter; or co-release GABA and glycine. However, the developmental relationship between GABAergic, glycinergic and cotransmitting neurons, and the functional relevance of cotransmitting neurons has remained enigmatic. Transgenic mice expressing fluorescent markers or the split-Cre system in inhibitory neurons were developed to track the three different interneuron phenotypes. During late embryonic development, the majority of inhibitory neurons in the ventrolateral medulla are cotransmitting cells, most of which differentiate into GABAergic and glycinergic neurons around birth and around postnatal day 4, respectively. Functional inactivation of cotransmitting neurons revealed an increase of the number of respiratory pauses, the cycle-by-cycle variability, and the overall variability of breathing. In summary, the majority of cotransmitting neurons differentiate into GABAergic or glycinergic neurons within the first 2 weeks after birth and these neurons contribute to fine-tuning of the breathing pattern."],["dc.identifier.doi","10.3389/fncel.2019.00517"],["dc.identifier.eissn","1662-5102"],["dc.identifier.pmid","31803026"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17103"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78488"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1662-5102"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","GABA-Glycine Cotransmitting Neurons in the Ventrolateral Medulla: Development and Functional Relevance for Breathing"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e24241"],["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Trevisiol, Andrea"],["dc.contributor.author","Saab, Aiman S."],["dc.contributor.author","Winkler, Ulrike"],["dc.contributor.author","Marx, Grit"],["dc.contributor.author","Imamura, Hiromi"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Kusch, Kathrin"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Hirrlinger, Johannes"],["dc.date.accessioned","2017-05-22T13:48:50Z"],["dc.date.accessioned","2021-10-27T13:21:00Z"],["dc.date.available","2017-05-22T13:48:50Z"],["dc.date.available","2021-10-27T13:21:00Z"],["dc.date.issued","2017"],["dc.description.abstract","In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders."],["dc.identifier.doi","10.7554/eLife.24241"],["dc.identifier.pmid","28414271"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14464"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91987"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","2050-084X"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Monitoring ATP dynamics in electrically active white matter tracts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]