Bernhard Reuss

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Prof. Dr. Bernhard Reuss
Location Göttingen
Position Professor
Tel. +49-(0)551/39-13770


    • 2017
    • Crossreactivity of an antiserum directed to the gram-negative bacterium Neisseria gonorrhoeae with the SNARE-complex protein Snap23 correlates to impaired exocytosis in SH-SY5Y cells.
      Almamy, A.; Schwerk, C.; Schroten, H.; Asif, A.R.; Reuss, B..
      Journal of Molecular Neuroscience, 2017. DOI 10.1007/s12031-017-0920-2

      Abstract Early maternal infections with Neisseriagonorrhoeae (NG) correlate to an increased lifetime schizophreniarisk for the offspring, which might be due to animmune-mediated mechanism. Here, we investigated the interactionsof polyclonal antisera to NG (α-NG) with a firsttrimester prenatal brain multiprotein array, revealing amongothers the SNARE-complex protein Snap23 as a target antigenfor α-NG. This interaction was confirmed by Western blotanalysis with a recombinant Snap23 protein, whereas theclosely related Snap25 failed to interact with α-NG.Furthermore, a polyclonal antiserum to the closely relatedbacterium Neisseria meningitidis (α-NM) failed tointeract with both proteins. Functionally, in SH-SY5Y cells,α-NG pretreatment interfered with both insulin-induced vesiclerecycling, as revealed by uptake of the fluorescent endocytosismarker FM1-43, and insulin-dependent membranetranslocation of the glucose transporter GluT4. Similar effectscould be observed for an antiserum raised directly to Snap23,whereas a serum to Snap25 failed to do so. In conclusion,Snap23 seems to be a possible immune target for antigonococcalantibodies, the interactions of which seem at leastin vitro to interfere with vesicle-associated exocytosis.Whether these changes contribute to the correlation betweenmaternal gonococcal infections and psychosis in vivo remainsstill to be clarified.

    • Interactions of antisera to different Chlamydia and Chlamydophila species with the ribosomal protein RPS27a correlate with impaired protein synthesis in a human choroid plexus papilloma cell line..
      Almamy A, Schwerk C, Schroten H, Ishikawa H, Asif AR, Reuss B.
      IMMUNOL RES 65(6): 1110-1123, doi: 10.1007/s12026-017-8952-9, 2017.

      Chlamydia trachomatis(CT) and theChlamydophilaspecies (CS)Chlamydophila pneumoniae(CPn), andChlamydophila psittaci(CPs) are suggested toinduce autoantibodies causative of several human autoim-mune disorders like rheumatoid arthritis and systemic lupuserythematosus (SLE). The aim of the present study was there-fore to identify cellular protein interaction partners withantisera to CT (α-CT) or CS (α-CS) and to identify functionalconsequences of such interaction in vitro. As detected with acommercial first trimester human prenatal brain multiproteinarray (hEXselect, Engine, Germany), the most frequent inter-action partner with bothα-CT andα-CS was the ribosomalsmall subunit protein RPS27a. This could be confirmed byWestern blot analysis with a recombinant RPS27a sample. Inaddition, immunocytochemistry with both antisera in the hu-man choroid plexus papilloma cell line HIBCPP revealed agranular cytoplasmic staining, and Western blot analysis withwhole-cell protein samples of HIBCPP cells revealed bothantisera to label protein bands of different molecular weightsand intensity. By 2D Western blot analysis and mass spec-trometry, one of the protein spots interacting withα-CT couldbe identified as the RPS27a. Finally, two different methods forthe detection of protein synthesis activity, the SUnSET tech-nique and an HPG fluorescence assay revealed both antiserato cause reduced translational activity in HIBCPP cells.Together with previous findings of RPS27a as an autoimmunetarget in a mouse model of systemic lupus erythematosus(SLE), these results suggest that infections with CT and/orCS could induce SLE-associated immune modifications.However, direct evidence for a pathogenic role of these inter-actions for SLE demands further investigations.

    • 2016
    • Antisera against Neisseria gonorrhoeae cross-react with specific brain proteins of the common marmoset monkey and other nonhuman primate species.
      Reuss, B.; Asif, A.R.; Almamy,A.; Schwerk, C.; Schroten, H.; Ishikawa, H.; Drummer, C.; Behr, R..
      Brain Research 1653:23-38, 2016. doi: 10.1016/j.brainres.2016.10.012
      abstract link

      Prenatal maternal infections with Neisseria gonorrhoeae (NG) correlate with an increased lifetime probability for the offspring to develop psychosis. We could previously demonstrate that in human choroid plexus papilloma cells, anti-NG antibodies (α-NG) bind to mitochondrial proteins HSP60 and ATPB, and interfere with cellular energy metabolism. To assess the in vivo relevance for this, especially during prenatal neural development, we investigated here interactions of NG-specific antisera (α-NG1, α-NG2) with brain, choroid plexus and other non-neural tissues in pre- and perinatal samples of the nonhuman primate (NHP) Callithrix jacchus (CJ), a NHP model for preclinical research. In histological sections at embryonic day E75, immunohistochemistry revealed α-NG1 and -2-staining in choroid plexus, ganglionic hill, optic cup, heart, and liver. Within the cells, organelle-like structures were labeled, which could be identified by immunohistochemical double-labeling as mitochondria. Both one- and two-dimensional Western blot analysis revealed tissue specific patterns of α-NG1 immunoreactive bands and spots, respectively, which were subsequently characterized by mass spectrometry. Thereby we could confirm the interactions of α-NG1 with human HSP60 and ATPB also in CJ choroid plexus and liver. Even more important, in the CJ brain, several new targets, including NCAM1, CRMP2, and SYT1, were identified, which by unrelated studies have been previously suggested to correlate with an increased schizophrenia risk. These findings support the idea that the marmoset monkey is a useful NHP model to investigate the role of maternal bacterial infections during prenatal brain development, and thereby might improve the understanding of this important aspect of schizophrenia pathology.

    • 2014
    • Impair Nerve Growth Factor-Dependent Neurite Outgrowth in Rat PC12 Cells.
      Reuss B..
      J Mol Neurosci, 2014.
      abstract link

      In children born from mothers with prenatal infections with the Gram-negative bacterium Neisseria gonorrhoeae, schizophrenia risk is increased in later life. Since cortical neuropil formation is frequently impaired during this disease, actions of a rabbit polyclonal antiserum directed to N. gonorrhoeae on neurite outgrowth in nerve growth factor-stimulated PC12 cells were investigated here. It turned out that 10 μg/ml of the antiserum leads indeed to a significant reduction in neurite outgrowth, whereas an antiserum directed to Neisseria meningitidis had no such effect. Furthermore, reduction in neurite outgrowth could be reversed by the neuroleptic drugs haloperidol, clozapine, risperidone, and olanzapine. On the molecular level, the observed effects seem to include the known neuritogenic transcription factors FoxO3a and Stat3, since reduced neurite outgrowth caused by the antiserum was accompanied by a reduced phosphorylation of both factors. In contrast, restitution of neurite outgrowth by neuroleptic drugs revealed no correlation to the phosphorylation state of these factors. The present report gives a first hint that bacterial infections could indeed lead to impaired neuropil formation in vitro; however, the in vivo relevance of this finding for schizophrenia pathogenesis remains to be clarified in the future.

    • Antibodies Directed to the Gram-Negative Bacterium Neisseria gonorrhoeae Cross-React with the 60 kDa Heat Shock Protein and Lead to Impaired Neurite Outgrowth in NTera2/D1 Cells.
      Reuss B., Asif A.R..
      J Mol Neurosci, 2014.
      abstract link

      Children of mothers with prenatal gonococcal infections are of increased risk to develop schizophrenic psychosis in later life. The present study hypothesizes an autoimmune mechanism for this, investigating interactions of a commercial rabbit antiserum directed to Neisseria gonorrhoeae (α-NG) with human NTera2/D1 cells, an established in vitro model for human neuronal differentiation. Immunocytochemistry demonstrated α-NG to label antigens on an intracellular organelle, which by Western blot analysis showed a molecular weight shortly below 72 kDa. An antiserum directed to Neisseria meningitidis (α-NM) reacts with an antigen shortly below 95 kDa, confirming antibody specificity of these interactions. Two-dimensional gel electrophoresis and partial Western transfer, allowed to localize an α-NG reactive protein spot which was identified by LC-Q-TOF MS/MS analysis as mitochondrial heat shock protein Hsp60. This was confirmed by Western blot analysis of α-NG immunoreactivity with a commercial Hsp60 protein sample, with which α-NM failed to interact. Finally, analysis of neurite outgrowth in retinoic acid-stimulated differentiating NTera2-D1 cells, demonstrates that α-NG but not α-NM treatment reduces neurite length. These results demonstrate that α-NG can interact with Hsp60 in vitro, whereas pathogenetic relevance of this interaction for psychotic symptomatology remains to be clarified.

    • 2010
    • Tamoxifen and raloxifene modulate gap junction coupling during early phases of retinoic acid-dependent neuronal differentiation of NTera2/D1 cells.
      Dahm L., Klugmann F., Gonzalez-Algaba a., Reuss B..
      Cell Biol Toxicol, 2010.
      abstract link

      Gap junctions (GJ) represent a cellular communication system known to influence neuronal differentiation and survival. To assess a putative role of this system for neural effects of tamoxifen (TAM) and raloxifene (RAL), we used the human teratocarcinoma cell line NTera2/D1, retinoic acid (RA)-dependent neuronal differentiation of which is regulated by gap junctions formed of connexin43 (Cx43). As demonstrated by Western blot analysis, concentrations above 1 µmol/l for TAM, and 0.1 µmol/l for RAL lead to a temporary time- and concentration-dependent increase in Cx43 immunoreactivity, which reached a peak for TAM after 1 day and for RAL after 2 days. Immunocytochemical stainings revealed the increase in Cx43 immunoreactivity to result from an accumulation in intracellular compartments such as the Golgi apparatus or lysosomes. In addition, TAM and RAL were able to prevent the RA-dependent decrease of Cx43 immunoreactivity in NTera2/D1 cells, normally observed during neuronal differentiation. This suggested a suppression of neuronal differentiation to result from these substances. According to this, treatment of NTera2/D1 cells with 10 µmol/l TAM or RAL during weeks 1 and 2 of a 6 weeks RA-driven differentiation schedule impaired, whereas treatment during weeks 5 and 6 did not impair, neuronal differentiation of these cells. Modulation of GJ coupling between NTera2/D1 cells by TAM and RAL seems therefore to perturb early neuronal differentiation, whereas differentiated neurons in the mature brain seem to be not affected. These effects could be of importance for actions of TAM and RAL on early embryonic steps of nervous system formation.