Heinrich, Ralf

[["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"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Knorr, Debbra Y."],["dc.contributor.author","Schneider, Kristin"],["dc.contributor.author","Büschgens, Luca"],["dc.contributor.author","Förster, Jan"],["dc.contributor.author","Georges, Nadine S."],["dc.contributor.author","Geurten, Bart R. H."],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2022-12-01T08:30:55Z"],["dc.date.available","2022-12-01T08:30:55Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n \n Cytokine receptor-like factor 3 (CRLF3) is a conserved but largely uncharacterized orphan cytokine receptor of eumetazoan animals. CRLF3-mediated neuroprotection in insects can be stimulated with human erythropoietin. To identify mechanisms of CRLF3-mediated neuroprotection we studied the expression and proapoptotic function of acetylcholinesterase in insect neurons. We exposed primary brain neurons from\n Tribolium castaneum\n to apoptogenic stimuli and dsRNA to interfere with acetylcholinesterase gene expression and compared survival and acetylcholinesterase expression in the presence or absence of the CRLF3 ligand erythropoietin. Hypoxia increased apoptotic cell death and expression of both acetylcholinesterase-coding genes\n ace-1\n and\n ace-2\n . Both\n ace\n genes give rise to single transcripts in normal and apoptogenic conditions. Pharmacological inhibition of acetylcholinesterases and RNAi-mediated knockdown of either\n ace-1\n or\n ace-2\n expression prevented hypoxia-induced apoptosis. Activation of CRLF3 with protective concentrations of erythropoietin prevented the increased expression of acetylcholinesterase with larger impact on\n ace-1\n than on\n ace-2\n . In contrast, high concentrations of erythropoietin that cause neuronal death induced\n ace-1\n expression and hence promoted apoptosis. Our study confirms the general proapoptotic function of AChE, assigns a role of both\n ace-1\n and\n ace-2\n in the regulation of apoptotic death and identifies the erythropoietin/CRLF3-mediated prevention of enhanced acetylcholinesterase expression under apoptogenic conditions as neuroprotective mechanism."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Georg-August-Universität Göttingen 501100003385"],["dc.identifier.doi","10.1038/s41598-022-22035-0"],["dc.identifier.pii","22035"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118016"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","2045-2322"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Protection of insect neurons by erythropoietin/CRLF3-mediated regulation of pro-apoptotic acetylcholinesterase"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1958"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","1963"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Versteven, Marijke"],["dc.contributor.author","Broeck, Lies Vanden"],["dc.contributor.author","Geurten, Bart R. H."],["dc.contributor.author","Zwarts, Liesbeth"],["dc.contributor.author","Decraecker, Lisse"],["dc.contributor.author","Beelen, Melissa"],["dc.contributor.author","Göpfert, Martin C."],["dc.contributor.author","Heinrich, Ralf"],["dc.contributor.author","Callaerts, Patrick"],["dc.date.accessioned","2018-11-07T10:27:16Z"],["dc.date.available","2018-11-07T10:27:16Z"],["dc.date.issued","2017"],["dc.description.abstract","Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level."],["dc.identifier.doi","10.1073/pnas.1605946114"],["dc.identifier.isi","000395099500074"],["dc.identifier.pmid","28115690"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43214"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Hearing regulates Drosophila aggression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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"]]

[["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"]]

[["dc.bibliographiccitation.firstpage","63"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","74"],["dc.bibliographiccitation.volume","141"],["dc.contributor.author","Miljus, Natasa"],["dc.contributor.author","Massih, Bita"],["dc.contributor.author","Weis, Marissa A."],["dc.contributor.author","Rison, Jan Vincent"],["dc.contributor.author","Bonnas, Christel B."],["dc.contributor.author","Sillaber, Inge"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Geurten, Bart R. H."],["dc.contributor.author","Heinrich, Ralf"],["dc.date.accessioned","2018-11-07T10:25:45Z"],["dc.date.available","2018-11-07T10:25:45Z"],["dc.date.issued","2017"],["dc.description.abstract","Erythropoietin (Epo) plays a dual role as an erythropoiesis-stimulating hormone and a locally produced cytoprotectant in various vertebrate tissues. Splice variants and engineered derivatives of Epo that mediate neuroprotection but do not stimulate erythropoiesis suggest that alternative receptors, different from the classical' homodimeric receptor involved in haematopoiesis, mediate neuroprotective Epo functions. Previous studies on grasshoppers demonstrated neuroprotective and neuroregenerative effects of Epo that involved similar transduction pathways as in mammals. To advance the characterization of yet unidentified neuroprotective Epo receptors, we studied the neuroprotective potency of the human non-erythropoietic Epo splice variant EV-3 in primary cultured locust brain neurons. We demonstrate that EV-3, like Epo, protects locust neurons from hypoxia-induced apoptotic death through activation of the Janus kinase/signal transducer and activator of transcription transduction pathway. Using the fluorescent dye FM1-43 to quantify endocytotic activity we show that both Epo and EV-3 increase the number of fluorescently labelled endocytotic vesicles. This reveals that binding of Epo to its neuroprotective receptor induces endocytosis, as it has been described for the mammalian homodimeric Epo-receptor expressed by erythroid progenitors. Reduction in Epo-stimulated endocytotic activity following pre-exposure to EV-3 indicated that both Epo and its splice variant bind to the same receptor on locust neurons. The shared neuroprotective potency of Epo and EV-3 in insect and mammalian neurons, in the absence of erythropoietic effects of EV-3 in mammals, suggests a greater similarity of the unidentified nervous Epo receptors (or receptor complexes) across phyla than between mammalian haematopoietic and neuroprotective receptors. Insects may serve as suitable models to evaluate the specific protective mechanisms mediated by Epo and its variants in non-erythropoietic mammalian tissues."],["dc.identifier.doi","10.1111/jnc.13967"],["dc.identifier.isi","000397502400006"],["dc.identifier.pmid","28142212"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42919"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.relation.issn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.title","Neuroprotection and endocytosis: erythropoietin receptors in insect nervous systems"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["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"]]