Schulz, Jörg Bernhard

[["dc.bibliographiccitation.firstpage","2"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuropathology and Experimental Neurology"],["dc.bibliographiccitation.lastpage","13"],["dc.bibliographiccitation.volume","73"],["dc.contributor.author","Tauber, Simone C."],["dc.contributor.author","Harms, Kristian"],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Weis, Joachim"],["dc.contributor.author","Sellhaus, Bernd"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Reich, Arno"],["dc.date.accessioned","2018-11-07T09:46:12Z"],["dc.date.available","2018-11-07T09:46:12Z"],["dc.date.issued","2014"],["dc.description.abstract","Fas-apoptotic inhibitory molecule 2 (Faim2) is a neuron-specific membrane protein and a member of the evolutionary conserved lifeguard apoptosis regulatory gene family. Its neuroprotective effect in acute neurological diseases has been demonstrated in an in vivo model of focal cerebral ischemia. Here we show that Faim2 is physiologically expressed in the human brain with a changing pattern in cases of infectious meningoencephalitis.In Faim2-deficient mice, there was increased caspase-associated hippocampal apoptotic cell death and an increased extracellular signal-regulated kinase pattern during acute bacterial meningitis induced by subarachnoid infection with Streptococcus pneumoniae type 3 strain. However, after rescuing the animals by antibiotic treatment, Faim2 deficiency led to increased hippocampal neurogenesis at 7 weeks after infection. This was associated with improved performance of Faim2-deficient mice compared to wild-type littermates in the Morris water maze, a paradigm for hippocampal spatial learning and memory. Thus, Faim2 deficiency aggravated degenerative processes in the acute phase but induced regenerative processes in the repair phase of a mouse model of pneumococcal meningitis. Hence, time-dependent modulation of neuroplasticity by Faim2 may offer a new therapeutic approach for reducing hippocampal neuronal cell death and improving cognitive deficits after bacterial meningitis."],["dc.identifier.doi","10.1097/NEN.0000000000000020"],["dc.identifier.isi","000335647400001"],["dc.identifier.pmid","24335530"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34817"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","0022-3069"],["dc.title","Modulation of Hippocampal Neuroplasticity by Fas/CD95 Regulatory Protein 2 (Faim2) in the Course of Bacterial Meningitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","20049"],["dc.bibliographiccitation.issue","50"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","20054"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Kowsky, Sebastian"],["dc.contributor.author","Poeppelmeyer, Charlotte"],["dc.contributor.author","Kramer, Edgar R."],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Kruse, Anja"],["dc.contributor.author","Klein, Ruediger"],["dc.contributor.author","Schulz, Joerg B."],["dc.date.accessioned","2018-11-07T10:45:12Z"],["dc.date.available","2018-11-07T10:45:12Z"],["dc.date.issued","2007"],["dc.description.abstract","Activation of the RET (rearranged during transfection) receptor by glial cell-line-derived neurotrophic factor (GDNF) has been identified as an important differentiation and survival factor for dopaminergic neurons of the midbrain in preclinical experiments. These encouraging results have led to clinical trials of GDNF in patients with Parkinson's disease, which have resulted in conflicting findings. To investigate the potential benefit of Ret-dependent signaling on the challenged dopaminergic system, we tested the effect of tissue-selective ablation of the Ret gene on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in mice, the most widely used animal model for Parkinson's disease. Ablation of Ret did not modify the MPTP-induced loss of dopaminergic neurons in the substantia nigra pars compacta and the dopaminergic innervation of the striatum at 14 days. However, Ret ablation abolished the regeneration of dopaminergic fibers and terminals, as well as the partial recovery of striatal dopamine concentrations, that was observed in control mice between days 14 and 90 after MPTP treatment. We therefore conclude that RET signaling has no influence on the survival of dopaminergic neurons in the MPTP model of Parkinson's disease but rather facilitates the regeneration of dopaminergic axon terminals."],["dc.identifier.doi","10.1073/pnas.0706177104"],["dc.identifier.isi","000251752200072"],["dc.identifier.pmid","18056810"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47446"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","RET signaling does not modulate MPTP toxicity but is required for regeneration of dopaminergic axon terminals"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","85"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neuropathology and Experimental Neurology"],["dc.bibliographiccitation.lastpage","94"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Schmidt, Anna Kathrin"],["dc.contributor.author","Reich, Arno"],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Brandenburg, Lars Ove"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Tauber, Simone C."],["dc.date.accessioned","2018-11-07T10:04:09Z"],["dc.date.available","2018-11-07T10:04:09Z"],["dc.date.issued","2015"],["dc.description.abstract","Despite the development of new antibiotic agents, mortality of pneumococcal meningitis remains high. In addition, meningitis results in severe long-term morbidity, most prominently cognitive deficits. Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation and differentiation of hematopoietic progenitor cells and increases the number of circulating neutrophil granulocytes. This study investigated the effect of adjuvant G-CSF treatment on cognitive function after pneumococcal meningitis. C57BL/6 mice were infected by subarachnoid injection of Streptococcus pneumoniae serotype 3 and treated with ceftriaxone and G-CSF subcutaneously or ceftriaxone alone for 5 days. Clinical scores, motor performance, and mortality during bacterial meningitis were unaffected by adjuvant G-CSF treatment. No effect of G-CSF treatment on production of proinflammatory cytokines or activation of microglia or astrocytes was observed. The G-CSF treatment did, however, result in hippocampal neurogenesis and improved spatial learning performance 6 weeks after meningitis. These results suggest that G-CSF might offer a new adjuvant therapeutic approach in bacterial meningitis to reduce long-term cognitive deficits."],["dc.description.sponsorship","Else Kroner-Fresenius-Stiftung [2010_A102]"],["dc.identifier.isi","000346634900008"],["dc.identifier.pmid","25470346"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38632"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1554-6578"],["dc.relation.issn","0022-3069"],["dc.title","Adjuvant Granulocyte Colony-Stimulating Factor Therapy Results in Improved Spatial Learning and Stimulates Hippocampal Neurogenesis in a Mouse Model of Pneumococcal Meningitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","135"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell and Tissue Research"],["dc.bibliographiccitation.lastpage","147"],["dc.bibliographiccitation.volume","318"],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.date.accessioned","2018-11-07T10:45:04Z"],["dc.date.available","2018-11-07T10:45:04Z"],["dc.date.issued","2004"],["dc.description.abstract","Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra leading to the major clinical and pharmacological abnormalities of PD. In order to establish causal or protective treatments for PD, it is necessary to identify the cascade of deleterious events that lead to the dysfunction and death of dopaminergic neurons. Based on genetic, neuropathological, and biochemical data in patients and experimental animal models, dysfunction of the ubiquitin-proteasome pathway, protein aggregation, mitochondrial dysfunction, oxidative stress, activation of the c-Jun N-terminal kinase pathway, and inflammation have all been identified as important pathways leading to excitotoxic and apoptotic death of dopaminergic neurons. Toxin-based and genetically engineered animal models allow (1) the study of the significance of these aspects and their interaction with each other and (2) the development of causal treatments to stop disease progression."],["dc.identifier.doi","10.1007/s00441-004-0954-y"],["dc.identifier.isi","000224618200016"],["dc.identifier.pmid","15365812"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/47410"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0302-766X"],["dc.title","Neuronal pathology in Parkinson's disease"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3256"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","3268"],["dc.bibliographiccitation.volume","28"],["dc.contributor.author","Karpinar, Damla Pinar"],["dc.contributor.author","Balija, Madhu Babu Gajula"],["dc.contributor.author","Kügler, Sebastian"],["dc.contributor.author","Opazo, Felipe"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Wender, Nora"],["dc.contributor.author","Kim, Hai-Young"],["dc.contributor.author","Taschenberger, Grit"],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Heise, Henrike"],["dc.contributor.author","Kumar, Ashutosh"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Fichtner, Lars"],["dc.contributor.author","Voigt, Aaron"],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Herzig, Alf"],["dc.contributor.author","Baldus, Marc"],["dc.contributor.author","Jaeckle, Herbert"],["dc.contributor.author","Eimer, Stefan"],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:46:48Z"],["dc.date.available","2017-09-07T11:46:48Z"],["dc.date.issued","2009"],["dc.description.abstract","The relation of alpha-synuclein (alpha S) aggregation to Parkinson's disease (PD) has long been recognized, but the mechanism of toxicity, the pathogenic species and its molecular properties are yet to be identified. To obtain insight into the function different aggregated alpha S species have in neurotoxicity in vivo, we generated alpha S variants by a structure-based rational design. Biophysical analysis revealed that the alpha S mutants have a reduced fibrillization propensity, but form increased amounts of soluble oligomers. To assess their biological response in vivo, we studied the effects of the biophysically defined pre-fibrillar alpha S mutants after expression in tissue culture cells, in mammalian neurons and in PD model organisms, such as Caenorhabditis elegans and Drosophila melanogaster. The results show a striking correlation between alpha S aggregates with impaired beta-structure, neuronal toxicity and behavioural defects, and they establish a tight link between the biophysical properties of multimeric aS species and their in vivo function. The EMBO Journal (2009) 28, 3256-3268. doi:10.1038/emboj.2009.257; Published online 10 September 2009"],["dc.identifier.doi","10.1038/emboj.2009.257"],["dc.identifier.gro","3143038"],["dc.identifier.isi","000271008200017"],["dc.identifier.pmid","19745811"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/508"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","Pre‐fibrillar α‐synuclein variants with impaired β‐structure increase neurotoxicity in Parkinson's disease models"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","261"],["dc.bibliographiccitation.lastpage","268"],["dc.bibliographiccitation.seriesnr","70"],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.editor","Riederer, P."],["dc.date.accessioned","2018-11-07T10:37:00Z"],["dc.date.available","2018-11-07T10:37:00Z"],["dc.date.issued","2006"],["dc.description.abstract","Cell cultures for Parkinson's disease research have the advantage of virtually unlimited access, they allow rapid screening for disease pathogenesis and drug candidates, and they restrict the necessary number of animal experiments. Limitations of cell cultures, include that the survival of neurons is dependent upon the culture conditions; that the cells do not develop their natural neuronal networks. In most cases, neurons are deprived from the physiological afferent and efferent connections. In Parkinson's disease research, mesencephalic slice cultures, primary immature doparninergic neurons and immortalized cell lines - either in a proliferating state or in a differentiated state - are used. Neuronal cultures may be plated in the presence or absence of glial cells and serum. These different culture conditions as well as the selection of outcome parameters (morphological evaluation, viability assays, biochemical assays, metabolic assays) have a strong influence on the results of the experiments and the conclusions drawn from them. A primary example is the question of whether L-Dopa is toxic to doparninergic neurons or whether it provides neurotrophic effects: In pure, neuronal-like cultures, L-Dopa provides toxicity, whereas in the presence of glial cells, it provides trophic effects when applied. The multitude of factors that influence the data generated from cell culture experiments indicates that in order to obtain clear-cut and unambiguous results, investigators need to choose their model carefully and are encouraged to verify their main results with different models."],["dc.identifier.isi","000240329000041"],["dc.identifier.pmid","17017539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45457"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","Wien"],["dc.relation.conference","16th International Congress on Parkinsons Disease and Related Disorders"],["dc.relation.crisseries","Journal of Neural Transmission. Supplementum"],["dc.relation.eventend","2005-06-09"],["dc.relation.eventlocation","Berlin, Germany"],["dc.relation.eventstart","2005-06-05"],["dc.relation.isbn","3-211-28927-5"],["dc.relation.isbn","978-3-211-28927-3"],["dc.relation.ispartof","Parkinson's disease and related disorders"],["dc.relation.ispartofseries","Journal of neural transmission. Supplementum; 70"],["dc.relation.issn","0303-6995"],["dc.title","Limitations of cellular models in Parkinson's disease research"],["dc.type","conference_paper"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1002488"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Butler, Erin K."],["dc.contributor.author","Voigt, Aaron"],["dc.contributor.author","Lutz, A. Kathrin"],["dc.contributor.author","Toegel, Jane Patricia"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Karsten, Peter"],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.contributor.author","Reinartz, Andrea"],["dc.contributor.author","Winklhofer, Konstanze F."],["dc.contributor.author","Schulz, Joerg B."],["dc.date.accessioned","2018-11-07T09:13:43Z"],["dc.date.available","2018-11-07T09:13:43Z"],["dc.date.issued","2012"],["dc.description.abstract","Overexpression or mutation of alpha-Synuclein is associated with protein aggregation and interferes with a number of cellular processes, including mitochondrial integrity and function. We used a whole-genome screen in the fruit fly Drosophila melanogaster to search for novel genetic modifiers of human [A53T] alpha-Synuclein-induced neurotoxicity. Decreased expression of the mitochondrial chaperone protein tumor necrosis factor receptor associated protein-1 (TRAP1) was found to enhance age-dependent loss of fly head dopamine (DA) and DA neuron number resulting from [A53T] alpha-Synuclein expression. In addition, decreased TRAP1 expression in [A53T] alpha-Synuclein-expressing flies resulted in enhanced loss of climbing ability and sensitivity to oxidative stress. Overexpression of human TRAP1 was able to rescue these phenotypes. Similarly, human TRAP1 overexpression in rat primary cortical neurons rescued [A53T] alpha-Synuclein-induced sensitivity to rotenone treatment. In human (non) neuronal cell lines, small interfering RNA directed against TRAP1 enhanced [A53T] alpha-Synuclein-induced sensitivity to oxidative stress treatment. [A53T] alpha-Synuclein directly interfered with mitochondrial function, as its expression reduced Complex I activity in HEK293 cells. These effects were blocked by TRAP1 overexpression. Moreover, TRAP1 was able to prevent alteration in mitochondrial morphology caused by [A53T] alpha-Synuclein overexpression in human SH-SY5Y cells. These results indicate that [A53T] alpha-Synuclein toxicity is intimately connected to mitochondrial dysfunction and that toxicity reduction in fly and rat primary neurons and human cell lines can be achieved using overexpression of the mitochondrial chaperone TRAP1. Interestingly, TRAP1 has previously been shown to be phosphorylated by the serine/threonine kinase PINK1, thus providing a potential link of PINK1 via TRAP1 to alpha-Synuclein."],["dc.identifier.doi","10.1371/journal.pgen.1002488"],["dc.identifier.isi","000300725500013"],["dc.identifier.pmid","22319455"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7775"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27236"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1553-7390"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","The Mitochondrial Chaperone Protein TRAP1 Mitigates alpha-Synuclein Toxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","529"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","540"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Opazo, Felipe"],["dc.contributor.author","Krenz, Antje"],["dc.contributor.author","Heermann, Stephan"],["dc.contributor.author","Schulz, Joerg B."],["dc.contributor.author","Falkenburger, Bjoern H."],["dc.date.accessioned","2018-11-07T11:13:37Z"],["dc.date.available","2018-11-07T11:13:37Z"],["dc.date.issued","2008"],["dc.description.abstract","Aggregates of alpha-synuclein are the pathological hallmark of sporadic Parkinson's disease (PD), and mutations in the alpha-synuclein gene underlie familial forms of the disease. To characterize the formation of alpha-synuclein aggregates in living cells, we developed a new strategy to visualize alpha-synuclein by fluorescence microscopy: alpha-synuclein was tagged with a six amino acid PDZ binding motif and co-expressed with the corresponding PDZ domain fused to enhanced green fluorescent protein (EGFP). In contrast to the traditional approach of alpha-synuclein-EGFP fusion proteins, this technique provided several-fold higher sensitivity; this allowed us to compare alpha-synuclein variants and perform time-lapse imaging. A C-terminally truncated alpha-synuclein variant showed the highest prevalence of aggregates and toxicity, consistent with stabilization of the alpha-synuclein monomer by its C-terminus. Time-lapse imaging illustrated how cells form and accumulate aggregates of alpha-synuclein. A substantial number of cells also reduced their aggregate load, primarily through formation of an aggresome, which could itself be cleared from the cell. The molecular chaperone Hsp70 not only prevented the formation of aggregates, but also increased their reduction and clearance, underlining the therapeutic potential of similar strategies. In contrast to earlier assumptions build-up, reduction and clearance of alpha-synuclein aggregation thus appear a highly dynamic process."],["dc.identifier.doi","10.1111/j.1471-4159.2008.05407.x"],["dc.identifier.isi","000257708000004"],["dc.identifier.pmid","18410502"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/53939"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Publishing"],["dc.relation.issn","0022-3042"],["dc.title","Accumulation and clearance of alpha-synuclein aggregates demonstrated by time-lapse imaging"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]