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.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.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"]]