Maler, Juan Manuel

[["dc.bibliographiccitation.firstpage","466"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Fortschritte der Neurologie · Psychiatrie"],["dc.bibliographiccitation.lastpage","475"],["dc.bibliographiccitation.volume","67"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Maler, Manuel"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Degner, Detlef"],["dc.contributor.author","Rüther, Eckart"],["dc.date.accessioned","2017-09-07T11:44:45Z"],["dc.date.available","2017-09-07T11:44:45Z"],["dc.date.issued","2008"],["dc.description.abstract","The spectrum of action of flupirtine includes analgesic, muscle-relaxant and neuroprotective properties. The substance's mechanism of action has yet to be fully explained. Over the past few years, however, evidence has accumulated that flupirtine interacts with the glutamatergic N-Methyl-D-Aspartate (NMDA) receptor. Although it was not possible to demonstrate a direct effect on the NMDA receptor, all of the findings pointed to an indirect influence on the NMDA receptor in the sense of a functional NMDA antagonism. It was thus postulated that a site of action \"up- or downstream\" of the NMDA receptor is influenced. Such a site of action proved to be the G-protein-activated inwardly rectifying K+ channels (GIRK), the opening of which leads to a stabilisation of the resting membrane potential of neuronal cells and thus causes an indirect inhibition of the NMDA receptor. At therapeutically relevant concentrations, flupirtine is a neuronal potassium channel opener. This mechanism may explain the spectrum of action of flupirtine. Selective neuronal potassium channel opening (SNEPCO) thus proves to be a new principle of action, making flupirtine the prototype of a new substance class with analgesic, muscle-relaxant and neuroprotective properties. The experimental basis for this working hypothesis and the resulting model concepts are presented from the perspective of a four-stage approach."],["dc.description.abstract","Das Wirkspektrum von Flupirtin umfaßt analgetische, muskelentspannende und neuroprotektive Eigenschaften. Der Wirkmechanismus der Substanz war bislang unzureichend bekannt. In den letzten Jahren verdichteten sich jedoch Hinweise auf eine Interaktion von Flupirtin mit dem glutamatergen N-Methyl-D-Aspartat (NMDA)-Rezeptor. Obwohl eine direkte Wirkung am NMDA-Rezeptor nicht nachweisbar war. sprachen alle Befunde für eine indirekte Beeinflussung des NMDA-Rezeptors im Sinne eines funktionellen NMDA-Antagonismus. Es wurde somit postuliert, daß ein Wirkort ,,up- oder downstream\" vom NMDA-Rezeptor beeinflußt wird. Als solcher erwiesen sich die G-Protein gesteuerten einwärts gleichrichtenden K\"-Kanale (GIRK), deren Öffnung zu einer Stabilisierung des Ruhemembranpotentials neuronaler Zellen führt und dadurch eine indirekte Hemmung des NMDA-Rezeptors bewirkt. Flupirtin ist in therapeutisch relevanten Konzentrationen ein neuronaler K'-Kanalöffner (neuronal potassium Channel opener). Dieser Mechanismus vermag das Wirkspektrum von Flupirtin zu erklären. Damit erweist sich die selektive neuronale K+-Kanaloffnung (SNEPCO) als ein neues Wirkprinzip und Flupirtin als Prototyp einer neuen Substanzklasse mit analgetischen, muskelrelaxierenden und neuroprotektiven Eigenschaften. Die experimentellen Grundlagen dieser Arbeitshypothese und der daraus resultierenden Modellvorstellungen werden in einer vierstufigen Betrachtungsebene vorgestellt."],["dc.identifier.doi","10.1055/s-2007-994997"],["dc.identifier.gro","3151740"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8561"],["dc.language.iso","de"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0720-4299"],["dc.title","Neuronale Kaliumkanalöffnung durch Flupirtin"],["dc.title.subtitle","Opening of Neuronal K+ Channels by Flupirtine"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","65"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Gerontology"],["dc.bibliographiccitation.lastpage","71"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Hüther, Gerald"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2017-09-07T11:44:43Z"],["dc.date.available","2017-09-07T11:44:43Z"],["dc.date.issued","2001"],["dc.description.abstract","Over the past few years, molecular biological research has considerably deepened our understanding of the pathophysiological basis of Alzheimer’s dementia (AD). Although different genetic origins of the disease have been identified, all of the findings point to a common terminal sequence in familial AD. This consists of an increased production of β-amyloid peptides from β-amyloid precursor protein. For the cases of sporadic AD, which far outweigh the number of cases of familial AD, an impaired catabolism of the β-amyloid peptides may also be pathophysiologically decisive according to the latest findings. Research into the molecular level of AD makes it possible to identify points of attack for rational drug treatment of the disease, while molecular markers of AD are increasingly being used as a part of early and differential neurochemical diagnostics."],["dc.identifier.doi","10.1159/000052775"],["dc.identifier.gro","3151719"],["dc.identifier.pmid","11287729"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8539"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0304-324X"],["dc.title","Molecular Biology of Alzheimer’s Dementia and Its Clinical Relevance to Early Diagnosis and New Therapeutic Strategies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","812"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","818"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Vanderstichele, Hugo"],["dc.contributor.author","Vanmechelen, Eugeen"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Wolf, Stefanie"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Reulbach, Udo"],["dc.contributor.author","Koelsch, Heike"],["dc.contributor.author","Jessen, Frank"],["dc.contributor.author","Schroeder, Johannes"],["dc.contributor.author","Schoenknecht, Peter"],["dc.contributor.author","Hampel, Harald"],["dc.contributor.author","Peters, Oliver"],["dc.contributor.author","Weimer, Erik"],["dc.contributor.author","Perneczky, Robert"],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Luckhaus, Christian"],["dc.contributor.author","Lamla, Ulrich"],["dc.contributor.author","Supprian, Tillmann"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2018-11-07T11:14:50Z"],["dc.date.available","2018-11-07T11:14:50Z"],["dc.date.issued","2008"],["dc.description.abstract","In this report we evaluated the clinical performance of APOE genotyping and three protein biomarkers (total tau, beta-amyloid(1-42), and tau phosphorylated at threonine 181) in a prospective multicenter study using the INNO-BIA AlzBio3 assay applied on Luminex platform, Concentration of biomarkers of Alzheimer's. disease in cerebrospinal fluid (CSF) was measured with multiplexing technology (n = 223), and compared to the results of ELISA assays in patients with early dementias or mild cognitive impairment (MCI) collected at 12 gerontopsychiatric university departments, and APOE genotyping was performed. Concentrations of A beta(1-42) were statistically significantly lower in MCI-AD subjects compared to MCI-O, and significantly lower in D-AD patients compared to MCI-O. P-tau(181P) concentrations were significantly higher in MCI-AD patients compared to MCI-O, and significantly higher in D-AD patients compared to MCI-O. The total tau concentrations in MCI-AD patients were significantly higher compared to MCI-O, and higher in D-AD compared to MCI-O, moreover, the concentration of total tau was significantly higher in D-AD compared to MCI-AD patients. For the differential diagnosis between D-AD and D-O, the optimal cutoff concentration of A beta(1-42) was 197.7pg/mL, and that for P-tau(181P) was 47.9pg/mL. These cutoff values were also applied to discriminate between MCI-AD and MCI-O subjects. Simultaneous measurement of the biomarkers significantly improves management of the samples and quality control of the assays' performance. (C) 2007 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.neurobiolaging.2006.12.010"],["dc.identifier.isi","000255599700002"],["dc.identifier.pmid","17239996"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54230"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0197-4580"],["dc.title","Multiplexed quantification of dementia biomarkers in the CSF of patients with early dementias and MCI: A multicenter study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Pharmacopsychiatry"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Esselmann, Herrmann"],["dc.contributor.author","Dyrks, T."],["dc.contributor.author","Klafki, H."],["dc.contributor.author","Fiszer, M."],["dc.contributor.author","Paul, S."],["dc.contributor.author","Reulbach, Udo"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Ruther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, J."],["dc.date.accessioned","2018-11-07T10:56:36Z"],["dc.date.available","2018-11-07T10:56:36Z"],["dc.date.issued","2005"],["dc.format.extent","262"],["dc.identifier.isi","000232591900164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50051"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Georg Thieme Verlag Kg"],["dc.publisher.place","Stuttgart"],["dc.relation.conference","24th Symposium of the Arbeitsgemeinschaft-fur-Neuropsychopharmakologie-und-Pharmakopsychiatrie (AGNP)"],["dc.relation.eventlocation","Munich, GERMANY"],["dc.relation.issn","0176-3679"],["dc.title","Specific inhibition of beta-amyloid peptide secretion by ZK808762 mimicks the effect of non-steroidal antiinflammatory drugs"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","273"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.lastpage","281"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Reulbach, Udo"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Henkel, Andreas Wolfram"],["dc.contributor.author","Henkel, Maria Kerstin"],["dc.contributor.author","Eikenberg, Oliver"],["dc.contributor.author","Antz, Christof"],["dc.contributor.author","Krause, Wolf-Rainer"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2018-11-07T10:50:56Z"],["dc.date.available","2018-11-07T10:50:56Z"],["dc.date.issued","2004"],["dc.description.abstract","Cerebrospinal fluid (CSF) concentrations of amyloid p peptides ending at positions 42 and 40 (Abeta42 and Abeta40, respectively), and total tau (tTau) protein were measured by ELISA in order to compare their accuracy in discriminating patients with Alzheimer's disease (AD, n = 22), non-Alzheimer dementia (nAD, n = 11) and control subjects (CON, n = 35). As compared to the other groups, the concentrations of Abeta42 and tTau were decreased (P < 0.001) and increased (P < 0.001) in AD, respectively, while Abeta40 did not differ significantly among the groups. Receiver operating characteristic (ROC) analysis was performed to define cut-off values for maximized sensitivity and specificity. For all groups compared the Abeta peptide ratio 42/40 classified more patients correctly, as compared to the concentration of Abeta42 alone: AD versus controls, 94 and 86.7%; AD versus nAD, 90 and 85% and AD versus nAD plus controls, 90.8 and 87%, respectively. The percentage of correctly classified patients was further improved when the Abeta ratio was combined with the analysis of the tTau concentration. Presence of the apolipoprotein E epsilon4 allele, age or degree of mental disability did not significantly influence the parameters studied. (C) 2003 Elsevier Science Inc. All rights reserved."],["dc.identifier.doi","10.1016/S0197-4580(03)00086-1"],["dc.identifier.gro","3151667"],["dc.identifier.isi","000189229600001"],["dc.identifier.pmid","15123331"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48765"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","0197-4580"],["dc.title","Neurochemical diagnosis of Alzheimer's dementia by CSF A beta 42, A beta 42/A beta 40 ratio and total tau"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","524"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Biological Psychiatry"],["dc.bibliographiccitation.lastpage","530"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Groemer, Teja Wolfgang"],["dc.contributor.author","Bibl, Mirko"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Steinacker, Petra"],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2017-09-07T11:44:28Z"],["dc.date.available","2017-09-07T11:44:28Z"],["dc.date.issued","2004"],["dc.description.abstract","The advent of new therapeutic avenues for Alzheimer's disease (AD) calls for an improved early and differential diagnosis. With surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), cerebrospinal fluid from patients with AD (n = 10) and nondemented control subjects (n = 9) was studied. Molecular mass signals were observed corresponding to three novel amyloid beta (Aβ) peptides that have not previously been described, in addition to those previously known, with molecular masses of 4525.1 d, 4846.8 d, and 7755.8 d. The signal-to-noise ratios (S/NR) of Aβ(4525.1) and Aβ(7758.8+2H) were significantly decreased in AD [Aβ(4525.1): median 2.2 and 4.3 in AD and control subjects, respectively, p < .01; Aβ(7758.8+2H): median 1.0 and 14.0 in AD and control subjects, respectively, p < .01], whereas the S/NR of Aβ(4846.8) was significantly increased in AD (median 3.6 and 2.5 in AD and control subjects, respectively, p < .05). The S/NR of two known AD biomarkers, Aβ1-42 and Aβ1-40, expectedly turned out to be significantly decreased (p < .01) and unaltered in AD, respectively. A moderate and highly significant correlation was observed between S/NR of Aβ1-42 and Aβ42 concentration as measured with enzyme-linked immunosorbent assay (R = .67, p < .01). We report evidence of three novel amyloid β peptides that might play an important role in the diagnosis and pathophysiology of Alzheimer's disease."],["dc.identifier.doi","10.1016/j.biopsych.2003.10.014"],["dc.identifier.gro","3151663"],["dc.identifier.pmid","15023581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8480"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0006-3223"],["dc.title","Amyloid β peptides in cerebrospinal fluid as profiled with surface enhanced laser desorption/ionization time-of-flight mass spectrometry: evidence of novel biomarkers in Alzheimer's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","156"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Brain Research"],["dc.bibliographiccitation.lastpage","162"],["dc.bibliographiccitation.volume","1052"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Esselmann, Herrmann"],["dc.contributor.author","Wiltfang, J."],["dc.contributor.author","Kunz, N."],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Reulbach, Udo"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Ruther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2018-11-07T10:56:49Z"],["dc.date.available","2018-11-07T10:56:49Z"],["dc.date.issued","2005"],["dc.description.abstract","The present study examined the effect of memantine, an uncompetitive NMDA receptor antagonist, on ethanol-induced NMDA receptor up-regulation. Primary glutamatergic rat hippocampal neurons were exposed to ethanol and memantine for 5 days. The ethanol-sensitive NMDA receptor subunits NR1, NR2A and NR213 were quantified by Western immunoblot analysis. Fxposure to ethanol (50 mM) caused an increase in the levels of NRI (137 +/- 11 % of untreated control, P = 0.009), NR2A (128 +/- 14 %. P 0.022) and N213 (136 +/- 119 %, P = 0.012). Coincubation with memantine (10 mu M) completely blocked the ethanol-induced up-regulation of NR1 (102, 4 %) NR2A (95 +/- 7 %) and NR2B (105 +/- 13 %). No effect of memantine on NR subunit expression was observable, except for NR2A, where a decrease (79 +/- 6 %, P = 0.034) was noted. Neither ethanol nor memantine alone or in combination were toxic in the concentrations tested. These results may provide a molecular explanation for beneficial effects of memantine on ethanol-induced glutamatergic hyperexcitability reflected in the ethanol withdrawal syndrome and on the development of ethanol dependence. (c) 2005 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.brainres.2005.06.017"],["dc.identifier.isi","000231493000005"],["dc.identifier.pmid","16009352"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50105"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0006-8993"],["dc.title","Mernantine inhibits ethanol-induced NMDA receptor up-regulation in rat hippocampal neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e1390"],["dc.bibliographiccitation.issue","15"],["dc.bibliographiccitation.journal","Neurology"],["dc.bibliographiccitation.lastpage","e1401"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Steinacker, Petra"],["dc.contributor.author","Anderl-Straub, Sarah"],["dc.contributor.author","Diehl-Schmid, Janine"],["dc.contributor.author","Semler, Elisa"],["dc.contributor.author","Uttner, Ingo"],["dc.contributor.author","von Arnim, Christine A.F."],["dc.contributor.author","Barthel, Henryk"],["dc.contributor.author","Danek, Adrian"],["dc.contributor.author","Fassbender, Klaus"],["dc.contributor.author","Fliessbach, Klaus"],["dc.contributor.author","Foerstl, Hans"],["dc.contributor.author","Grimmer, Timo"],["dc.contributor.author","Huppertz, Hans-Jürgen"],["dc.contributor.author","Jahn, Holger"],["dc.contributor.author","Kassubek, Jan"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Landwehrmeyer, Bernhard"],["dc.contributor.author","Lauer, Martin"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Mayer, Benjamin"],["dc.contributor.author","Oeckl, Patrick"],["dc.contributor.author","Prudlo, Johannes"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Volk, Alexander E."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Schroeter, Matthias L."],["dc.contributor.author","Ludolph, Albert C."],["dc.contributor.author","Otto, Markus"],["dc.date.accessioned","2020-12-10T18:41:45Z"],["dc.date.available","2020-12-10T18:41:45Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1212/WNL.0000000000006318"],["dc.identifier.eissn","1526-632X"],["dc.identifier.issn","0028-3878"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77663"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Serum neurofilament light chain in behavioral variant frontotemporal dementia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","236"],["dc.bibliographiccitation.issue","4-5"],["dc.bibliographiccitation.journal","Neurodegenerative Diseases"],["dc.bibliographiccitation.lastpage","241"],["dc.bibliographiccitation.volume","1"],["dc.contributor.author","Esselmann, Hermann"],["dc.contributor.author","Maler, J. M."],["dc.contributor.author","Kunz, N."],["dc.contributor.author","Otto, Markus"],["dc.contributor.author","Paul, S."],["dc.contributor.author","Lewczuk, Piotr"],["dc.contributor.author","Rüther, Eckart"],["dc.contributor.author","Kornhuber, Johannes"],["dc.contributor.author","Wiltfang, Jens"],["dc.date.accessioned","2017-09-07T11:44:27Z"],["dc.date.available","2017-09-07T11:44:27Z"],["dc.date.issued","2004"],["dc.description.abstract","We studied endogenous amyloid precursor protein (APP) processing and amyloid beta (Aβ) peptide formation in primary chicken telencephalic neurons, because their Aβ peptide sequence is identical to humans. As detected by quantitative Aβ-SDS-PAGE/immunoblot, Aβ peptides 1–40/42 and three additional C-truncated species, namely Aβ1–37/38/39 were regularly released into the supernatant. The highly conserved Aβ quintet strongly resembles the pattern of Aβ peptides found in human cerebrospinal fluid. Furthermore, the C-terminally shorter Aβ peptides 1–33/34 could be readily detected. Recent evidence indicates that lithium specifically inhibits secretion of the amyloidogenic Aβ1–42 peptide in cultured permanent cells transfected with human APP. We therefore investigated the effect of lithium on Aβ peptide secretion as well as intracellular Aβ peptides in our untransfected primary cell culture system. Our data shows that lithium leads to a dose-dependent reduction of Aβ1–37/38/39/40/42 secretion. Surprisingly, intracellular analysis revealed that lithium specifically increases a band comigrating with synthetic Aβ1–38 while Aβ1–40 and Aβ1–42 remained almost unaffected. These results demonstrate for the first time that lithium treatment decreases Aβ peptide secretion in primary chicken neuronal cells but specifically elevates intracellular Aβ1–38. Therefore, we conclude that there are two independent mechanisms of lithium in intra- and extracellular Aβ peptide production."],["dc.identifier.doi","10.1159/000080992"],["dc.identifier.gro","3151670"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8488"],["dc.language.iso","en"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","chake"],["dc.relation.issn","1660-2854"],["dc.title","Lithium Decreases Secretion of Aβ1–42 and C-Truncated Species Aβ1–37/38/39/40 in Chicken Telencephalic Cultures but Specifically Increases Intracellular Aβ1–38"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","56"],["dc.bibliographiccitation.issue","SH2"],["dc.bibliographiccitation.journal","Fortschritte der Neurologie · Psychiatrie"],["dc.bibliographiccitation.lastpage","61"],["dc.bibliographiccitation.volume","69"],["dc.contributor.author","Bleich, Stefan"],["dc.contributor.author","Bleich, K."],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Maler, Juan Manuel"],["dc.contributor.author","Kornhuber, Johannes"],["dc.date.accessioned","2017-09-07T11:44:45Z"],["dc.date.available","2017-09-07T11:44:45Z"],["dc.date.issued","2002"],["dc.description.abstract","Glutamat ist der wichtigste erregende Neurotransmitter im zentralen Nervensystem. Es gibt Hinweise darauf, dass seine Aktivität bei schizophrenen Patienten vermindert, an anderen Stellen vermehrt ist. In den letzten Jahren wurden mit epidemiologischen, genetischen, histopathologischen und bildgebenden Untersuchungen deutliche Fortschritte in der Aufklärung der Krankheitsursachen erreicht und es wurden zunehmend integrative Modelle zur Pathogenese und Pathophysiologie schizophrener Psychosen entwickelt. Wenngleich auch verschiedene Vulnerabilitätsfaktoren und Stressoren zur Manifestation von schizophrenen Psychosen führen können, bildet die Glutamathypothese mit dem Modell eines kortiko-striato-thalamo-kortikalen Regelkreises weiterhin eine interessante Grundlage und bietet auch künftig zahlreiche Forschungsansätze, insbesondere in der weiteren Aufklärung der Affektion von Glutamatrezeptoren (z. B. NMDA-Rezeptoren), der glutamatergen Transmission sowie deren pharmakologische Beeinflussbarkeit. Glutamate is the most abundant amino acid in the brain, where it plays an important role as a well-established major excitatory neurotransmitter in the central nervous system. It has been suggested that reduced glutamate neurotransmission may be involved in the pathophysiology of schizophrenia. The glutamate hypothesis of schizophrenia postulates alterations in the glutamatergic system as an important neurobiochemical event in the pathophysiology of this group of psychotic disorders. An altered glutamate release from synaptosomes including a hypofunction of different glutamate receptors (i.e. NMDA receptors) from different brain areas have previously been reported. Furthermore, partial agonists at the glycine co-agonist site of the NMDA receptor might be a new approach in the treatment of schizophrenic symptoms but further studies are necessary to clarify the role and efficacy of these substances in schizophrenia. Changes in the glutamatergic cortico-striatal connections in schizophrenia could precipitate a potential perceptive overstimulation of the neocortex from thalamic input and an inhibiting influence of the striatum on the thalamus would modulate the information input of the cortex, thereby possibly counteracting the disturbed information processing which is relatively characteristic for schizophrenic psychoses."],["dc.identifier.doi","10.1055/s-2001-16531"],["dc.identifier.gro","3151738"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8559"],["dc.language.iso","de"],["dc.notes.status","final"],["dc.notes.submitter","chake"],["dc.relation.issn","0720-4299"],["dc.title","Glutamaterge Neurotransmission bei Schizophrenien"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]