Medrihan, Lucian

[["dc.bibliographiccitation.firstpage","5095"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","5106"],["dc.bibliographiccitation.volume","587"],["dc.contributor.author","Medrihan, Lucian"],["dc.contributor.author","Rohlmann, Astrid"],["dc.contributor.author","Fairless, Richard"],["dc.contributor.author","Andrae, Johanna"],["dc.contributor.author","Doring, Markus"],["dc.contributor.author","Missler, Markus"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Kilimann, Manfred W."],["dc.date.accessioned","2018-11-07T11:22:55Z"],["dc.date.available","2018-11-07T11:22:55Z"],["dc.date.issued","2009"],["dc.description.abstract","The development of neuronal networks in the brain requires the differentiation of functional synapses. Neurobeachin (Nbea) was identified as a putative regulator of membrane protein trafficking associated with tubulovesicular endomembranes and postsynaptic plasma membranes. Nbea is essential for evoked transmission at neuromuscular junctions, but its role in the central nervous system has not been characterized. Here, we have studied central synapses of a newly generated gene-trap knockout (KO) mouse line at embryonic day 18, because null-mutant mice are paralysed and die perinatally. Although the overall brain architecture was normal, we identified major abnormalities of synaptic function in mutant animals. In acute slices from the brainstem, both spontaneous excitatory and inhibitory postsynaptic currents were clearly reduced and failure rates of evoked inhibitory responses were markedly increased. In addition, the frequency of miniature excitatory and both the frequency and amplitudes of miniature inhibitory postsynaptic currents were severely diminished in KO mice, indicating a perturbation of both action potential-dependent and -independent transmitter release. Moreover, Nbea appears to be important for the formation and composition of central synapses because the area density of mature asymmetric contacts in the fetal brainstem was reduced to 30% of wild-type levels, and the expression levels of a subset of synaptic marker proteins were smaller than in littermate controls. Our data demonstrate for the first time a function of Nbea at central synapses that may be based on its presumed role in targeting membrane proteins to synaptic contacts, and are consistent with the 'excitatory-inhibitory imbalance' model of autism where Nbea gene rearrangements have been detected in some patients."],["dc.identifier.doi","10.1113/jphysiol.2009.178236"],["dc.identifier.isi","000271416900016"],["dc.identifier.pmid","19723784"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56077"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.relation.issn","0022-3751"],["dc.title","Neurobeachin, a protein implicated in membrane protein traffic and autism, is required for the formation and functioning of central synapses"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","112"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Neurophysiology"],["dc.bibliographiccitation.lastpage","121"],["dc.bibliographiccitation.volume","99"],["dc.contributor.author","Medrihan, Lucian"],["dc.contributor.author","Tantalaki, Evangelia"],["dc.contributor.author","Aramuni, Gayane"],["dc.contributor.author","Sargsyan, Vardanush"],["dc.contributor.author","Dudanova, Irina"],["dc.contributor.author","Missler, Markus"],["dc.contributor.author","Zhang, W."],["dc.date.accessioned","2018-11-07T11:20:15Z"],["dc.date.available","2018-11-07T11:20:15Z"],["dc.date.issued","2008"],["dc.description.abstract","Rett syndrome is a neurodevelopmental disorder caused by mutations in the transcriptional repressor methyl-CpG- binding protein 2 (MeCP2) and represents the leading genetic cause for mental retardation in girls. MeCP2-mutant mice have been generated to study the molecular mechanisms of the disease. It was suggested that an imbalance between excitatory and inhibitory neurotransmission is responsible for the behavioral abnormalities, although it remained largely unclear which synaptic components are affected and how cellular impairments relate to the time course of the disease. Here, we report that MeCP2 KO mice present an imbalance between inhibitory and excitatory synaptic transmission in the ventrolateral medulla already at postnatal day 7. Focusing on the inhibitory synaptic transmission we show that GABAergic, but not glycinergic, synaptic transmission is strongly depressed in MeCP2 KO mice. These alterations are presumably due to both decreased presynaptic gamma-aminobutyric acid (GABA) release with reduced levels of the vesicular inhibitory transmitter transporter and reduced levels of postsynaptic GABA(A)-receptor subunits alpha 2 and alpha 4. Our data indicate that in the MeCP2 -/y mice specific synaptic molecules and signaling pathways are impaired in the brain stem during early postnatal development. These observations mandate the search for more refined diagnostic tools and may provide a rationale for the timing of future therapeutic interventions in Rett patients."],["dc.identifier.doi","10.1152/jn.00826.2007"],["dc.identifier.isi","000252398500010"],["dc.identifier.pmid","18032561"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55490"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Physiological Soc"],["dc.relation.issn","0022-3077"],["dc.title","Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]