Ehrenreich, Hannelore

[["dc.bibliographiccitation.firstpage","136"],["dc.bibliographiccitation.journal","Neurobiology of Learning and Memory"],["dc.bibliographiccitation.lastpage","150"],["dc.bibliographiccitation.volume","150"],["dc.contributor.author","Dere, Ekrem"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Tampe, Björn"],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Schmidt, Manuela"],["dc.contributor.author","Zeisberg, Elisabeth"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2020-12-10T15:20:34Z"],["dc.date.available","2020-12-10T15:20:34Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.nlm.2018.02.023"],["dc.identifier.issn","1074-7427"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72715"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Cognitive, emotional and social phenotyping of mice in an observer-independent setting"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Molecular Psychiatry"],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Wilke, Justus B. H."],["dc.contributor.author","Seelbach, Anna"],["dc.contributor.author","Doeren, José"],["dc.contributor.author","Hindermann, Martin"],["dc.contributor.author","Butt, Umer Javed"],["dc.contributor.author","Steixner-Kumar, Agnes A."],["dc.contributor.author","Spieth, Lena"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Pan, Hong"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2022-01-11T14:05:41Z"],["dc.date.available","2022-01-11T14:05:41Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Encephalitis has an estimated prevalence of ≤0.01%. Even with extensive diagnostic work-up, an infectious etiology is identified or suspected in <50% of cases, suggesting a role for etiologically unclear, noninfectious processes. Mild encephalitis runs frequently unnoticed, despite slight neuroinflammation detectable postmortem in many neuropsychiatric illnesses. A widely unexplored field in humans, though clearly documented in rodents, is genetic brain inflammation, particularly that associated with myelin abnormalities, inducing primary white matter encephalitis. We hypothesized that “autoimmune encephalitides” may result from any brain inflammation concurring with the presence of brain antigen-directed autoantibodies, e.g., against N-methyl-D-aspartate-receptor NR1 (NMDAR1-AB), which are not causal of, but may considerably shape the encephalitis phenotype. We therefore immunized young female Cnp −/− mice lacking the structural myelin protein 2′-3′-cyclic nucleotide 3′-phosphodiesterase (Cnp) with a “cocktail” of NMDAR1 peptides. Cnp −/− mice exhibit early low-grade inflammation of white matter tracts and blood–brain barrier disruption. Our novel mental-time-travel test disclosed that Cnp −/− mice are compromised in what–where–when orientation, but this episodic memory readout was not further deteriorated by NMDAR1-AB. In contrast, comparing wild-type and Cnp −/− mice without/with NMDAR1-AB regarding hippocampal learning/memory and motor balance/coordination revealed distinct stair patterns of behavioral pathology. To elucidate a potential contribution of oligodendroglial NMDAR downregulation to NMDAR1-AB effects, we generated conditional NR1 knockout mice. These mice displayed normal Morris water maze and mental-time-travel, but beam balance performance was similar to immunized Cnp −/− . Immunohistochemistry confirmed neuroinflammation/neurodegeneration in Cnp −/− mice, yet without add-on effect of NMDAR1-AB. To conclude, genetic brain inflammation may explain an encephalitic component underlying autoimmune conditions."],["dc.description.abstract","Abstract Encephalitis has an estimated prevalence of ≤0.01%. Even with extensive diagnostic work-up, an infectious etiology is identified or suspected in <50% of cases, suggesting a role for etiologically unclear, noninfectious processes. Mild encephalitis runs frequently unnoticed, despite slight neuroinflammation detectable postmortem in many neuropsychiatric illnesses. A widely unexplored field in humans, though clearly documented in rodents, is genetic brain inflammation, particularly that associated with myelin abnormalities, inducing primary white matter encephalitis. We hypothesized that “autoimmune encephalitides” may result from any brain inflammation concurring with the presence of brain antigen-directed autoantibodies, e.g., against N-methyl-D-aspartate-receptor NR1 (NMDAR1-AB), which are not causal of, but may considerably shape the encephalitis phenotype. We therefore immunized young female Cnp −/− mice lacking the structural myelin protein 2′-3′-cyclic nucleotide 3′-phosphodiesterase (Cnp) with a “cocktail” of NMDAR1 peptides. Cnp −/− mice exhibit early low-grade inflammation of white matter tracts and blood–brain barrier disruption. Our novel mental-time-travel test disclosed that Cnp −/− mice are compromised in what–where–when orientation, but this episodic memory readout was not further deteriorated by NMDAR1-AB. In contrast, comparing wild-type and Cnp −/− mice without/with NMDAR1-AB regarding hippocampal learning/memory and motor balance/coordination revealed distinct stair patterns of behavioral pathology. To elucidate a potential contribution of oligodendroglial NMDAR downregulation to NMDAR1-AB effects, we generated conditional NR1 knockout mice. These mice displayed normal Morris water maze and mental-time-travel, but beam balance performance was similar to immunized Cnp −/− . Immunohistochemistry confirmed neuroinflammation/neurodegeneration in Cnp −/− mice, yet without add-on effect of NMDAR1-AB. To conclude, genetic brain inflammation may explain an encephalitic component underlying autoimmune conditions."],["dc.identifier.doi","10.1038/s41380-021-01392-8"],["dc.identifier.pii","1392"],["dc.identifier.pmid","34866134"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/97725"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/55"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-507"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease"],["dc.relation.eissn","1476-5578"],["dc.relation.issn","1359-4184"],["dc.relation.workinggroup","RG Ehrenreich (Clinical Neuroscience)"],["dc.relation.workinggroup","RG Nave (Neurogenetics)"],["dc.title","NMDAR1 autoantibodies amplify behavioral phenotypes of genetic white matter inflammation: a mild encephalitis model with neuropsychiatric relevance"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Molecular Psychiatry"],["dc.contributor.author","Butt, Umer Javed"],["dc.contributor.author","Steixner-Kumar, Agnes A."],["dc.contributor.author","Depp, Constanze"],["dc.contributor.author","Sun, Ting"],["dc.contributor.author","Hassouna, Imam"],["dc.contributor.author","Wüstefeld, Liane"],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Zillmann, Matthias R."],["dc.contributor.author","Schopf, Nadine"],["dc.contributor.author","Fernandez Garcia-Agudo, Laura"],["dc.contributor.author","Mohrmann, Leonie"],["dc.contributor.author","Bode, Ulli"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Hindermann, Martin"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Katschinski, Dörthe M."],["dc.contributor.author","Miskowiak, Kamilla W."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2021-04-14T08:28:40Z"],["dc.date.available","2021-04-14T08:28:40Z"],["dc.date.issued","2021"],["dc.description.abstract","Physical activity and cognitive challenge are established non-invasive methods to induce comprehensive brain activation and thereby improve global brain function including mood and emotional well-being in healthy subjects and in patients. However, the mechanisms underlying this experimental and clinical observation and broadly exploited therapeutic tool are still widely obscure. Here we show in the behaving brain that physiological (endogenous) hypoxia is likely a respective lead mechanism, regulating hippocampal plasticity via adaptive gene expression. A refined transgenic approach in mice, utilizing the oxygen-dependent degradation (ODD) domain of HIF-1α fused to CreERT2 recombinase, allows us to demonstrate hypoxic cells in the performing brain under normoxia and motor-cognitive challenge, and spatially map them by light-sheet microscopy, all in comparison to inspiratory hypoxia as strong positive control. We report that a complex motor-cognitive challenge causes hypoxia across essentially all brain areas, with hypoxic neurons particularly abundant in the hippocampus. These data suggest an intriguing model of neuroplasticity, in which a specific task-associated neuronal activity triggers mild hypoxia as a local neuron-specific as well as a brain-wide response, comprising indirectly activated neurons and non-neuronal cells."],["dc.identifier.doi","10.1038/s41380-020-00988-w"],["dc.identifier.pmid","33564132"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82678"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/31"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/104"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | Z02: Integrative Datenanalyse und -interpretation. Generierung einer synaptisch-integrativen Datenstrategie (SynIDs)"],["dc.relation.eissn","1476-5578"],["dc.relation.issn","1359-4184"],["dc.relation.workinggroup","RG Ehrenreich (Clinical Neuroscience)"],["dc.relation.workinggroup","RG Nave (Neurogenetics)"],["dc.relation.workinggroup","RG Bonn"],["dc.rights","CC BY 4.0"],["dc.title","Hippocampal neurons respond to brain activity with functional hypoxia"],["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","734"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","745"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Balmuth, Evan"],["dc.contributor.author","Mitjans, Marina"],["dc.contributor.author","Hertel, Johannes"],["dc.contributor.author","Habes, Mohamad"],["dc.contributor.author","Bittner, Robert A."],["dc.contributor.author","Pan, Hong"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Gerwig, Ulrike C."],["dc.contributor.author","Langner, Sönke"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Kittel-Schneider, Sarah"],["dc.contributor.author","Homuth, Georg"],["dc.contributor.author","Davatzikos, Christos"],["dc.contributor.author","Völzke, Henry"],["dc.contributor.author","West, Brian L."],["dc.contributor.author","Reif, Andreas"],["dc.contributor.author","Grabe, Hans Jörgen"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2020-12-10T18:38:19Z"],["dc.date.available","2020-12-10T18:38:19Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1172/JCI97032"],["dc.identifier.eissn","1558-8238"],["dc.identifier.issn","0021-9738"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77272"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Microglia ablation alleviates myelin-associated catatonic signs in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","121"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Wilke, Justus B. H."],["dc.contributor.author","Hindermann, Martin"],["dc.contributor.author","Moussavi, Amir"],["dc.contributor.author","Butt, Umer J."],["dc.contributor.author","Dadarwal, Rakshit"],["dc.contributor.author","Berghoff, Stefan A."],["dc.contributor.author","Sarcheshmeh, Aref K."],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Zihsler, Svenja"],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Hardeland, Rüdiger"],["dc.contributor.author","Seidel, Jan"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Boretius, Susann"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2021-11-25T11:24:44Z"],["dc.date.accessioned","2022-08-18T12:41:08Z"],["dc.date.available","2021-11-25T11:24:44Z"],["dc.date.available","2022-08-18T12:41:08Z"],["dc.date.issued","2021-07-02"],["dc.date.updated","2022-07-29T12:18:38Z"],["dc.description.abstract","Abstract\r\n Up to one person in a population of 10,000 is diagnosed once in lifetime with an encephalitis, in 50–70% of unknown origin. Recognized causes amount to 20–50% viral infections. Approximately one third of affected subjects develops moderate and severe subsequent damage. Several neurotropic viruses can directly infect pyramidal neurons and induce neuronal death in cortex and hippocampus. The resulting encephalitic syndromes are frequently associated with cognitive deterioration and dementia, but involve numerous parallel and downstream cellular and molecular events that make the interpretation of direct consequences of sudden pyramidal neuronal loss difficult. This, however, would be pivotal for understanding how neuroinflammatory processes initiate the development of neurodegeneration, and thus for targeted prophylactic and therapeutic interventions. Here we utilized adult male NexCreERT2xRosa26-eGFP-DTA (= ‘DTA’) mice for the induction of a sterile encephalitis by diphtheria toxin-mediated ablation of cortical and hippocampal pyramidal neurons which also recruits immune cells into gray matter. We report multifaceted aftereffects of this defined process, including the expected pathology of classical hippocampal behaviors, evaluated in Morris water maze, but also of (pre)frontal circuit function, assessed by prepulse inhibition. Importantly, we modelled in encephalitis mice novel translationally relevant sequelae, namely altered social interaction/cognition, accompanied by compromised thermoreaction to social stimuli as convenient readout of parallel autonomic nervous system (dys)function. High resolution magnetic resonance imaging disclosed distinct abnormalities in brain dimensions, including cortical and hippocampal layering, as well as of cerebral blood flow and volume. Fluorescent tracer injection, immunohistochemistry and brain flow cytometry revealed persistent blood–brain-barrier perturbance and chronic brain inflammation. Surprisingly, blood flow cytometry showed no abnormalities in circulating major immune cell subsets and plasma high-mobility group box 1 (HMGB1) as proinflammatory marker remained unchanged. The present experimental work, analyzing multidimensional outcomes of direct pyramidal neuronal loss, will open new avenues for urgently needed encephalitis research."],["dc.identifier.citation","Acta Neuropathologica Communications. 2021 Jul 02;9(1):121"],["dc.identifier.doi","10.1186/s40478-021-01214-6"],["dc.identifier.pii","1214"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112989"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.publisher","BioMed Central"],["dc.relation.eissn","2051-5960"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.subject","Diphtheria toxin"],["dc.subject","Hippocampal learning and memory"],["dc.subject","(pre)frontal network dysfunction"],["dc.subject","Social cognition"],["dc.subject","Thermography"],["dc.subject","Magnetic resonance imaging"],["dc.title","Inducing sterile pyramidal neuronal death in mice to model distinct aspects of gray matter encephalitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Molecular Psychiatry"],["dc.contributor.author","Wilke, Justus B. H."],["dc.contributor.author","Hindermann, Martin"],["dc.contributor.author","Berghoff, Stefan A."],["dc.contributor.author","Zihsler, Svenja"],["dc.contributor.author","Arinrad, Sahab"],["dc.contributor.author","Ronnenberg, Anja"],["dc.contributor.author","Barnkothe, Nadine"],["dc.contributor.author","Steixner-Kumar, Agnes A."],["dc.contributor.author","Röglin, Stefan"],["dc.contributor.author","Stöcker, Winfried"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2021-09-01T06:42:25Z"],["dc.date.available","2021-09-01T06:42:25Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The etiology and pathogenesis of “anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis” and the role of autoantibodies (AB) in this condition are still obscure. While NMDAR1-AB exert NMDAR-antagonistic properties by receptor internalization, no firm evidence exists to date that NMDAR1-AB by themselves induce brain inflammation/encephalitis. NMDAR1-AB of all immunoglobulin classes are highly frequent across mammals with multiple possible inducers and boosters. We hypothesized that “NMDAR encephalitis” results from any primary brain inflammation coinciding with the presence of NMDAR1-AB, which may shape the encephalitis phenotype. Thus, we tested whether following immunization with a “cocktail” of 4 NMDAR1 peptides, induction of a spatially and temporally defined sterile encephalitis by diphtheria toxin-mediated ablation of pyramidal neurons (“DTA” mice) would modify/aggravate the ensuing phenotype. In addition, we tried to replicate a recent report claiming that immunizing just against the NMDAR1-N368/G369 region induced brain inflammation. Mice after DTA induction revealed a syndrome comprising hyperactivity, hippocampal learning/memory deficits, prefrontal cortical network dysfunction, lasting blood brain-barrier impairment, brain inflammation, mainly in hippocampal and cortical regions with pyramidal neuronal death, microgliosis, astrogliosis, modest immune cell infiltration, regional atrophy, and relative increases in parvalbumin-positive interneurons. The presence of NMDAR1-AB enhanced the hyperactivity (psychosis-like) phenotype, whereas all other readouts were identical to control-immunized DTA mice. Non-DTA mice with or without NMDAR1-AB were free of any encephalitic signs. Replication of the reported NMDAR1-N368/G369-immunizing protocol in two large independent cohorts of wild-type mice completely failed. To conclude, while NMDAR1-AB can contribute to the behavioral phenotype of an underlying encephalitis, induction of an encephalitis by NMDAR1-AB themselves remains to be proven."],["dc.description.abstract","Abstract The etiology and pathogenesis of “anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis” and the role of autoantibodies (AB) in this condition are still obscure. While NMDAR1-AB exert NMDAR-antagonistic properties by receptor internalization, no firm evidence exists to date that NMDAR1-AB by themselves induce brain inflammation/encephalitis. NMDAR1-AB of all immunoglobulin classes are highly frequent across mammals with multiple possible inducers and boosters. We hypothesized that “NMDAR encephalitis” results from any primary brain inflammation coinciding with the presence of NMDAR1-AB, which may shape the encephalitis phenotype. Thus, we tested whether following immunization with a “cocktail” of 4 NMDAR1 peptides, induction of a spatially and temporally defined sterile encephalitis by diphtheria toxin-mediated ablation of pyramidal neurons (“DTA” mice) would modify/aggravate the ensuing phenotype. In addition, we tried to replicate a recent report claiming that immunizing just against the NMDAR1-N368/G369 region induced brain inflammation. Mice after DTA induction revealed a syndrome comprising hyperactivity, hippocampal learning/memory deficits, prefrontal cortical network dysfunction, lasting blood brain-barrier impairment, brain inflammation, mainly in hippocampal and cortical regions with pyramidal neuronal death, microgliosis, astrogliosis, modest immune cell infiltration, regional atrophy, and relative increases in parvalbumin-positive interneurons. The presence of NMDAR1-AB enhanced the hyperactivity (psychosis-like) phenotype, whereas all other readouts were identical to control-immunized DTA mice. Non-DTA mice with or without NMDAR1-AB were free of any encephalitic signs. Replication of the reported NMDAR1-N368/G369-immunizing protocol in two large independent cohorts of wild-type mice completely failed. To conclude, while NMDAR1-AB can contribute to the behavioral phenotype of an underlying encephalitis, induction of an encephalitis by NMDAR1-AB themselves remains to be proven."],["dc.identifier.doi","10.1038/s41380-021-01238-3"],["dc.identifier.pii","1238"],["dc.identifier.pmid","34331009"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89050"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/39"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | C01: Oligodendroglial NMDA receptors and NMDAR1 autoantibodies as determinants of axonal integrity in neuropsychiatric disease"],["dc.relation.eissn","1476-5578"],["dc.relation.issn","1359-4184"],["dc.relation.workinggroup","RG Ehrenreich (Clinical Neuroscience)"],["dc.relation.workinggroup","RG Nave (Neurogenetics)"],["dc.title","Autoantibodies against NMDA receptor 1 modify rather than cause encephalitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]