Tantra, Martesa

[["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","159"],["dc.bibliographiccitation.journal","Behavioural Brain Research"],["dc.bibliographiccitation.lastpage","164"],["dc.bibliographiccitation.volume","270"],["dc.contributor.author","Ju, Anes"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Krueger, Dilja"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:27Z"],["dc.date.available","2017-09-07T11:46:27Z"],["dc.date.issued","2014"],["dc.description.abstract","Neuroligin-4 (Nlgn4) is a member of the neuroligin family of postsynaptic cell adhesion molecules. Lossof-function mutations of NLGN4 are among the most frequent, known genetic causes of heritable autism.Adult Nlgn4 null mutant (Nlgn4−/−) mice are a construct valid model of human autism, with both gendersdisplaying a remarkable autistic phenotype, including deficits in social interaction and communication aswell as restricted and repetitive behaviors. In contrast to adults, autism-related abnormalities in neonataland juvenile Nlgn4−/− mice have not been reported yet. The present study has been designed tosystematically investigate in male and female Nlgn4−/− pups versus wildtype littermates (WT, Nlgn4+/+)developmental milestones and stimulus-induced ultrasound vocalization (USV). Neonatal development,followed daily from postnatal days (PND) 4 to 21, including physical development, neurological reflexesand neuromotor coordination, did not yield any differences between Nlgn4−/− and their WT littermates.USV in pups (PND8–9) in response to brief separation from their mothers revealed remarkable gendereffects, and a genotype influence in females regarding latency to first call. In juveniles (PND22–23),USV monitoring upon exposure to an anesthetized female intruder mouse uncovered a clear genotypeeffect with reduced USV in Nlgn4−/− mice, and again a more prominent phenotype in females. Together,these data support an early manifestation of communication deficits in Nlgn4−/− mice that appear morepronounced in immature females with their overall stronger USV as compared to males."],["dc.identifier.doi","10.1016/j.bbr.2014.05.019"],["dc.identifier.gro","3150517"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7290"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.subject","Neuroligin-4; C57BL/6J; Ultrasound or ultrasonic vocalization; Neonatal milestones; Neonatal development; Gender"],["dc.title","Juvenile manifestation of ultrasound communication deficits in the neuroligin-4 null mutant mouse model of autism"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","662"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","684"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Tantra, Martesa"],["dc.contributor.author","Hammer, Christian"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Dahm, Liane"],["dc.contributor.author","Begemann, Martin"],["dc.contributor.author","Bodda, Chiranjeevi"],["dc.contributor.author","Hammerschmidt, Kurt"],["dc.contributor.author","Giegling, Ina"],["dc.contributor.author","Stepniak, Beata"],["dc.contributor.author","Castillo Venzor, Aracely"],["dc.contributor.author","Konte, Bettina"],["dc.contributor.author","Erbaba, Begun"],["dc.contributor.author","Hartmann, Annette M."],["dc.contributor.author","Tarami, Asieh"],["dc.contributor.author","Schulz-Schaeffer, Walter J."],["dc.contributor.author","Rujescu, Dan"],["dc.contributor.author","Mannan, Ashraf U."],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.date.accessioned","2017-09-07T11:46:35Z"],["dc.date.available","2017-09-07T11:46:35Z"],["dc.date.issued","2014"],["dc.description.abstract","The X-chromosomal MECP2/Mecp2 gene encodes methyl-CpG-binding protein 2, a transcriptional activator and repressor regulating many other genes. We discovered in male FVB/N mice that mild (~50%) transgenic overexpression of Mecp2 enhances aggression. Surprisingly, when the same transgene was expressed in C57BL/6N mice, transgenics showed reduced aggression and social interaction. This suggests that Mecp2 modulates aggressive social behavior. To test this hypothesis in humans, we performed a phenotype-based genetic association study (PGAS) in >1000 schizophrenic individuals. We found MECP2 SNPs rs2239464 (G/A) and rs2734647 (C/T; 3'UTR) associated with aggression, with the G and C carriers, respectively, being more aggressive. This finding was replicated in an independent schizophrenia cohort. Allele-specific MECP2 mRNA expression differs in peripheral blood mononuclear cells by ~50% (rs2734647: C > T). Notably, the brain-expressed, species-conserved miR-511 binds to MECP2 3'UTR only in T carriers, thereby suppressing gene expression. To conclude, subtle MECP2/Mecp2 expression alterations impact aggression. While the mouse data provides evidence of an interaction between genetic background and mild Mecp2 overexpression, the human data convey means by which genetic variation affects MECP2 expression and behavior."],["dc.identifier.doi","10.1002/emmm.201303744"],["dc.identifier.gro","3150551"],["dc.identifier.pmid","24648499"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11691"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7325"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Mild expression differences of MECP2 influencing aggressive social behavior"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]