Dahm, Liane

[["dc.bibliographiccitation.artnumber","181"],["dc.bibliographiccitation.journal","Frontiers in Behavioral Neuroscience"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Dere, Ekrem"],["dc.contributor.author","Dahm, Liane"],["dc.contributor.author","Lu, Derek"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Ju, Anes"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Chowdhury, Kamal"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:34Z"],["dc.date.available","2017-09-07T11:46:34Z"],["dc.date.issued","2014"],["dc.description.abstract","Autism-spectrum disorders (ASD) are heterogeneous, highly heritable neurodevelopmental conditions affecting around 0.5% of the population across cultures, with a male/female ratio of approximately 4:1. Phenotypically, ASD are characterized by social interaction and communication deficits, restricted interests, repetitive behaviors, and reduced cognitive flexibility. Identified causes converge at the level of the synapse, ranging from mutation of synaptic genes to quantitative alterations in synaptic protein expression, e.g., through compromised transcriptional or translational control. We wondered whether reduced turnover and degradation of synapses, due to deregulated autophagy, would lead to similar phenotypical consequences. Ambra1, strongly expressed in cortex, hippocampus, and striatum, is a positive regulator of Beclin1, a principal player in autophagosome formation. While homozygosity of the Ambra1 null mutation causes embryonic lethality, heterozygous mice with reduced Ambra1 expression are viable, reproduce normally, and lack any immediately obvious phenotype. Surprisingly, comprehensive behavioral characterization of these mice revealed an autism-like phenotype in Ambra1 (+/-) females only, including compromised communication and social interactions, a tendency of enhanced stereotypies/repetitive behaviors, and impaired cognitive flexibility. Reduced ultrasound communication was found in adults as well as pups, which achieved otherwise normal neurodevelopmental milestones. These features were all absent in male Ambra1 (+/-) mice. As a first hint explaining this gender difference, we found a much stronger reduction of Ambra1 protein in the cortex of Ambra1 (+/-) females compared to males. To conclude, Ambra1 deficiency can induce an autism-like phenotype. The restriction to the female gender of autism-generation by a defined genetic trait is unique thus far and warrants further investigation."],["dc.format.extent","19"],["dc.identifier.doi","10.3389/fnbeh.2014.00181"],["dc.identifier.gro","3150538"],["dc.identifier.pmid","24904333"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11695"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7311"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.subject","Ambra1; autism composite score; autophagy; cognitive rigidity; heterozygous null mutant mice; repetitive behavior; social interaction; ultrasound communication"],["dc.title","Heterozygous Ambra1 deficiency in mice: a genetic trait with autism-like behavior restricted to the female gender"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1180"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Stroke"],["dc.bibliographiccitation.lastpage","1186"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Zerche, M."],["dc.contributor.author","Weißenborn, Karin"],["dc.contributor.author","Ott, C."],["dc.contributor.author","Dere, Ekrem"],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Worthmann, Hans"],["dc.contributor.author","Hassouna, I."],["dc.contributor.author","Rentzsch, Katrin"],["dc.contributor.author","Tryc, A. B."],["dc.contributor.author","Dahm, Liane"],["dc.contributor.author","Steiner, Johann"],["dc.contributor.author","Binder, Lutz"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Sirén, A.-L."],["dc.contributor.author","Stöcker, W."],["dc.contributor.author","Ehrenreich, Hanhelore"],["dc.date.accessioned","2017-09-07T11:44:23Z"],["dc.date.available","2017-09-07T11:44:23Z"],["dc.date.issued","2015"],["dc.description.abstract","Background and Purpose—Recently, we reported high seroprevalence (age-dependent up to >19%) of N-methyl-d-aspartate-receptor subunit NR1 (NMDAR1) autoantibodies in both healthy and neuropsychiatrically ill subjects (N=4236). Neuropsychiatric syndrome relevance was restricted to individuals with compromised blood–brain barrier, for example, apolipoprotein E4 (APOE4) carrier status, both clinically and experimentally. We now hypothesized that these autoantibodies may upon stroke be protective in individuals with hitherto intact blood–brain barrier, but harmful for subjects with chronically compromised blood–brain barrier.Methods—Of 464 patients admitted with acute ischemic stroke in the middle cerebral artery territory, blood for NMDAR1 autoantibody measurements and APOE4 carrier status as indicator of a preexisting leaky blood–brain barrier was collected within 3 to 5 hours after stroke. Evolution of lesion size (delta day 7–1) in diffusion-weighted magnetic resonance imaging was primary outcome parameter. In subgroups, NMDAR1 autoantibody measurements were repeated on days 2 and 7.Results—Of all 464 patients, 21.6% were NMDAR1 autoantibody–positive (immunoglobulin M, A, or G) and 21% were APOE4 carriers. Patients with magnetic resonance imaging data available on days 1 and 7 (N=384) were divided into 4 groups according to NMDAR1 autoantibody and APOE4 status. Groups were comparable in all stroke-relevant presenting characteristics. The autoantibody+/APOE4− group had a smaller mean delta lesion size compared with the autoantibody−/APOE4- group, suggesting a protective effect of circulating NMDAR1 autoantibodies. In contrast, the autoantibody+/APOE4+ group had the largest mean delta lesion area. NMDAR1 autoantibody serum titers dropped on day 2 and remounted by day 7.Conclusions—Dependent on blood–brain barrier integrity before an acute ischemic brain injury, preexisting NMDAR1 autoantibodies seem to be beneficial or detrimental."],["dc.identifier.doi","10.1161/strokeaha.114.008323"],["dc.identifier.gro","3151637"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8453"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0039-2499"],["dc.title","Preexisting Serum Autoantibodies Against the NMDAR Subunit NR1 Modulate Evolution of Lesion Size in Acute Ischemic Stroke"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]