Now showing 1 - 6 of 6
  • 2017Journal Article
    [["dc.bibliographiccitation.journal","Frontiers in Psychiatry"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Corthals, Kristina"],["dc.contributor.author","Heukamp, Alina Sophia"],["dc.contributor.author","Kossen, Robert"],["dc.contributor.author","Großhennig, Isabel"],["dc.contributor.author","Hahn, Nina"],["dc.contributor.author","Gras, Heribert"],["dc.contributor.author","Göpfert, Martin C."],["dc.contributor.author","Heinrich, Ralf"],["dc.contributor.author","Geurten, Bart R. H."],["dc.date.accessioned","2019-07-09T11:43:34Z"],["dc.date.available","2019-07-09T11:43:34Z"],["dc.date.issued","2017"],["dc.description.abstract","The genome of Drosophila melanogaster includes homologs to approximately one-third of the currently known human disease genes. Flies and humans share many biological processes, including the principles of information processing by excitable neurons, synaptic transmission, and the chemical signals involved in intercellular communication. Studies on the molecular and behavioral impact of genetic risk factors of human neuro- developmental disorders [autism spectrum disorders (ASDs), schizophrenia, attention deficit hyperactivity disorders, and Tourette syndrome] increasingly use the well-studied social behavior of D. melanogaster, an organism that is amenable to a large variety of genetic manipulations. Neuroligins (Nlgs) are a family of phylogenetically conserved postsynaptic adhesion molecules present (among others) in nematodes, insects, and mammals. Impaired function of Nlgs (particularly of Nlg 3 and 4) has been associated with ASDs in humans and impaired social and communication behavior in mice. Making use of a set of behavioral and social assays, we, here, analyzed the impact of two Drosophila Nlgs, Dnlg2 and Dnlg4, which are differentially expressed at excitatory and inhibitory central nervous synapses, respectively. Both Nlgs seem to be associated with diurnal activity and social behavior. Even though deficiencies in Dnlg2 and Dnlg4 appeared to have no effects on sensory or motor systems, they differentially impacted on social interactions, suggesting that social behavior is distinctly regulated by these Nlgs."],["dc.identifier.doi","10.3389/fpsyt.2017.00113"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14580"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58919"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-0640"],["dc.relation.issn","1664-0640"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","570"],["dc.title","Neuroligins Nlg2 and Nlg4 Affect Social Behavior in Drosophila melanogaster"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
    Details DOI
  • 2017Journal Article
    [["dc.bibliographiccitation.artnumber","223"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Hahn, Nina"],["dc.contributor.author","Knorr, Debbra Y."],["dc.contributor.author","Liebig, Johannes"],["dc.contributor.author","Wüstefeld, Liane"],["dc.contributor.author","Peters, Karsten"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Heinrich, Ralf"],["dc.contributor.author","Büscher, Marita"],["dc.contributor.author","Bucher, Gregor"],["dc.date.accessioned","2018-03-08T09:22:14Z"],["dc.date.available","2018-03-08T09:22:14Z"],["dc.date.issued","2017"],["dc.description.abstract","The cytokine erythropoietin (Epo) mediates various cell homeostatic responses to environmental challenges and pathological insults. While stimulation of vertebrate erythrocyte production is mediated by homodimeric “classical” Epo receptors, alternative receptors are involved in neuroprotection. However, their identity remains enigmatic due to complex cytokine ligand and receptor interactions and conflicting experimental results. Besides the classical Epo receptor, the family of type I cytokine receptors also includes the poorly characterized orphan cytokine receptor-like factor 3 (CRLF3) present in vertebrates including human and various insect species. By making use of the more simple genetic makeup of insect model systems, we studied whether CRLF3 is a neuroprotective Epo receptor in animals. We identified a single ortholog of CRLF3 in the beetle Tribolium castaneum, and established protocols for primary neuronal cell cultures from Tribolium brains and efficient in vitro RNA interference. Recombinant human Epo as well as the non-erythropoietic Epo splice variant EV-3 increased the survival of serum-deprived brain neurons, confirming the previously described neuroprotective effect of Epo in insects. Moreover, Epo completely prevented hypoxia-induced apoptotic cell death of primary neuronal cultures. Knockdown of CRLF3 expression by RNA interference with two different double stranded RNA (dsRNA) fragments abolished the neuroprotective effect of Epo, indicating that CRLF3 is a crucial component of the insect Epo-responsive receptor. This suggests that a common urbilaterian ancestor of the orphan human and insect cytokine receptor CRLF3 served as a neuroprotective receptor for an Epo-like cytokine. Our work also suggests that vertebrate CRLF3, like its insect ortholog, might represent a tissue protection-mediating receptor."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.3389/fnmol.2017.00223"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14838"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/12916"],["dc.language.iso","en"],["dc.notes.intern","GRO-Li-Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.publisher","Frontiers Media S.A."],["dc.relation.doi","10.3389/fnmol.2017.00223"],["dc.relation.eissn","1662-5099"],["dc.relation.issn","1662-5099"],["dc.relation.issn","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The Insect Ortholog of the Human Orphan Cytokine Receptor CRLF3 Is a Neuroprotective Erythropoietin Receptor"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
    Details DOI
  • 2019Journal Article
    [["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Hahn, Nina"],["dc.contributor.author","Büschgens, Luca"],["dc.contributor.author","Schwedhelm-Domeyer, Nicola"],["dc.contributor.author","Bank, Sarah"],["dc.contributor.author","Geurten, Bart R. H."],["dc.contributor.author","Neugebauer, Pia"],["dc.contributor.author","Massih, Bita"],["dc.contributor.author","Göpfert, Martin C."],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2020-12-10T18:44:35Z"],["dc.date.available","2020-12-10T18:44:35Z"],["dc.date.issued","2019"],["dc.description.abstract","The orphan cytokine receptor-like factor 3 (CRLF3) was identified as a neuroprotective erythropoietin receptor in locust neurons and emerged with the evolution of the eumetazoan nervous system. Human CRLF3 belongs to class I helical cytokine receptors that mediate pleiotropic cellular reactions to injury and diverse physiological challenges. It is expressed in various tissues including the central nervous system but its ligand remains unidentified. A CRLF3 ortholog in the holometabolous beetle Tribolium castaneum was recently shown to induce anti-apoptotic mechanisms upon stimulation with human recombinant erythropoietin. To test the hypothesis that CRLF3 represents an ancient cell-protective receptor for erythropoietin-like cytokines, we investigated its presence across metazoan species. Furthermore, we examined CRLF3 expression and function in the hemimetabolous insect Locusta migratoria. Phylogenetic analysis of CRLF3 sequences indicated that CRLF3 is absent in Porifera, Placozoa and Ctenophora, all lacking the traditional nervous system. However, it is present in all major eumetazoan groups ranging from cnidarians over protostomians to mammals. The CRLF3 sequence is highly conserved and abundant amongst vertebrates. In contrast, relatively few invertebrates express CRLF3 and these sequences show greater variability, suggesting frequent loss due to low functional importance. In L. migratoria, we identified the transcript Lm-crlf3 by RACE-PCR and detected its expression in locust brain, skeletal muscle and hemocytes. These findings correspond to the ubiquitous expression of crlf3 in mammalian tissues. We demonstrate that the sole addition of double-stranded RNA to the culture medium (called soaking RNA interference) specifically interferes with protein expression in locust primary brain cell cultures. This technique was used to knock down Lm-crlf3 expression and to abolish its physiological function. We confirmed that recombinant human erythropoietin rescues locust brain neurons from hypoxia-induced apoptosis and showed that this neuroprotective effect is absent after knocking down Lm-crlf3. Our results affirm the erythropoietin-induced neuroprotective function of CRLF3 in a second insect species from a different taxonomic group. They suggest that the phylogenetically conserved CRLF3 receptor may function as a cell protective receptor for erythropoietin or a structurally related cytokine also in other animals including vertebrate and mammalian species."],["dc.identifier.doi","10.3389/fnmol.2019.00251"],["dc.identifier.eissn","1662-5099"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16484"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78513"],["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","1662-5099"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The Orphan Cytokine Receptor CRLF3 Emerged With the Origin of the Nervous System and Is a Neuroprotective Erythropoietin Receptor in Locusts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
    Details DOI
  • 2013Journal Article
    [["dc.bibliographiccitation.journal","Behavioural Brain Research"],["dc.bibliographiccitation.volume","256"],["dc.contributor.author","Hahn, Nina"],["dc.contributor.author","Geurten, Bart R. H."],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Piepenbrock, David"],["dc.contributor.author","Kaestner, Anne"],["dc.contributor.author","Zanini, Damiano"],["dc.contributor.author","Xing, Guanglin"],["dc.contributor.author","Xie, Wei"],["dc.contributor.author","Göpfert, Martin C."],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2018-11-07T09:17:53Z"],["dc.date.available","2018-11-07T09:17:53Z"],["dc.date.issued","2013"],["dc.format.extent","690"],["dc.identifier.doi","10.1016/j.bbr.2013.08.019"],["dc.identifier.isi","000328094100084"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28278"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1872-7549"],["dc.relation.issn","0166-4328"],["dc.title","Monogenic heritable autism gene neuroligin impacts Drosophila social behaviour (vol 252, pg 450, 2013)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details DOI WOS
  • 2015Conference Abstract
    [["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","American Journal of Hematology"],["dc.bibliographiccitation.volume","90"],["dc.contributor.author","Hahn, Nina"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2018-11-07T09:53:58Z"],["dc.date.available","2018-11-07T09:53:58Z"],["dc.date.issued","2015"],["dc.format.extent","E160"],["dc.identifier.isi","000358483700021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36439"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1096-8652"],["dc.relation.issn","0361-8609"],["dc.title","Erythropoietin in insects: receptors, signaling pathways and neuroprotection"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
    Details WOS
  • 2013Journal Article
    [["dc.bibliographiccitation.firstpage","450"],["dc.bibliographiccitation.journal","Behavioural Brain Research"],["dc.bibliographiccitation.lastpage","457"],["dc.bibliographiccitation.volume","252"],["dc.contributor.author","Hahn, Nina"],["dc.contributor.author","Geurten, Bart"],["dc.contributor.author","Gurvich, Artem"],["dc.contributor.author","Piepenbrock, David"],["dc.contributor.author","Kästner, Anne"],["dc.contributor.author","Zanini, Damiano"],["dc.contributor.author","Xing, Guanglin"],["dc.contributor.author","Xie, Wei"],["dc.contributor.author","Göpfert, Martin C."],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2017-09-07T11:46:23Z"],["dc.date.available","2017-09-07T11:46:23Z"],["dc.date.issued","2013"],["dc.description.abstract","Autism spectrum disorders (ASDs) are characterized by deficits in social interactions, language development and repetitive behaviours. Multiple genes involved in the formation, specification and maintenance of synapses have been identified as risk factors for ASDs development. Among these are the neuroligin genes which code for postsynaptic cell adhesion molecules that induce the formation of presynapses, promote their maturation and modulate synaptic functions in both vertebrates and invertebrates. Neuroligin-deficient mice display abnormal social and vocal behaviours that resemble ASDs symptoms.Here we show for the fly Drosophila melanogaster that deletion of the dnl2 gene, coding for one of four Neuroligin isoforms, impairs social interactions, alters acoustic communication signals, and affects the transition between different behaviours. dnl2-Deficient flies maintain larger distances to conspecifics and males perform less female-directed courtship and male-directed aggressive behaviours while the patterns of these behaviours and general locomotor activity were not different from wild type controls. Since tests for olfactory, visual and auditory perception revealed no sensory impairments of dnl2-deficient mutants, reduced social interactions seem to result from altered excitability in central nervous neuropils that initiate social behaviours. Our results demonstrate that Neuroligins are phylogenetically conserved not only regarding their structure and direct function at the synapse but also concerning a shared implication in the regulation of social behaviours that dates back to common ancestors of humans and flies. In addition to previously described mouse models, Drosophila can thus be used to study the contribution of Neuroligins to synaptic function, social interactions and their implication in ASDs."],["dc.identifier.doi","10.1016/j.bbr.2013.06.020"],["dc.identifier.gro","3150491"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7261"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.subject","Drosophila melanogaster; Neuroligin; Social behaviour; Acoustic communication; Behavioural transition; Autism"],["dc.title","Monogenic heritable autism gene neuroligin impacts Drosophila social behaviour"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]
    Details DOI