<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Excitotoxicity and NMDA receptor-mediated\r\nacquired neuroprotection in human iPSC-derived\r\nbrain organoids"^^ . "Excitotoxic cell death, resulting from excess brain glutamate and mediated predominantly\r\nthrough NMDA receptors (NMDARs), is implicated in various acute and chronic pathological\r\nconditions of the human brain, such as stroke, traumatic brain injury and neurodegenerative\r\ndiseases. In contrast, physiological NMDAR activation renders rodent neurons more resistant\r\nto potentially toxic stressors - a mechanism referred to as acquired neuroprotection. It is,\r\nhowever, not known whether such a dual action of NMDAR-signalling also exists human\r\nneurons.\r\nThis study employed human induced pluripotent stem cell-derived forebrain organoids to\r\ninvestigate NMDAR-mediated pro-death and pro-survival signalling in human neurons.\r\nExposure of forebrain organoids to high concentrations of NMDA caused an excitotoxic\r\ncascade involving loss of plasma membrane potential, cessation of synaptic activity, shut-off\r\nof the transcription factor CREB, induction of death-promoting P53 expression, structural\r\ndisintegration and ultimately cell death. In contrast, treatment of brain organoids with low\r\ndoses of NMDA triggered enhanced synaptic activity and survival-promoting signalling\r\nincluding the CREB phosphorylation and the expression of neuroprotective genes. This\r\ncondition, if applied as a pre-treatment, protected organoids against excitotoxic insults within\r\na defined time window. Surprisingly, the protective mechanism relied solely on the activation\r\nof NMDARs per se and occurred independently of the concomitant synaptic activation.\r\nMoreover, application of established as well as newly developed drugs to combat excitotoxicity\r\nprotected human forebrain organoids against NMDA-induced cell death.\r\nThe findings presented here show that many aspects of the dual action of NMDAR-signalling,\r\nincluding NMDAR-mediated acquired neuroprotection, are preserved in human neurons. The\r\nforebrain organoid methodology established here may serve as a platform for the development\r\nand testing of drugs counteracting excitotoxic cell death arising, for example, from acute\r\ncerebrovascular ischaemia and neurodegenerative diseases in humans."^^ . "2021" . . . . . . . "Hanke Gwendolyn"^^ . "Bauersachs"^^ . "Hanke Gwendolyn Bauersachs"^^ . . . . . . "Excitotoxicity and NMDA receptor-mediated\r\nacquired neuroprotection in human iPSC-derived\r\nbrain organoids (Other)"^^ . . . . . . "small.jpg"^^ . . . "Excitotoxicity and NMDA receptor-mediated\r\nacquired neuroprotection in human iPSC-derived\r\nbrain organoids (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Excitotoxicity and NMDA receptor-mediated\r\nacquired neuroprotection in human iPSC-derived\r\nbrain organoids (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Excitotoxicity and NMDA receptor-mediated\r\nacquired neuroprotection in human iPSC-derived\r\nbrain organoids (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Excitotoxicity and NMDA receptor-mediated\r\nacquired neuroprotection in human iPSC-derived\r\nbrain organoids (PDF)"^^ . . . "Dissertation_Bauersachs.pdf"^^ . . . "Excitotoxicity and NMDA receptor-mediated\r\nacquired neuroprotection in human iPSC-derived\r\nbrain organoids (Other)"^^ . . . . . . "medium.jpg"^^ . . "HTML Summary of #30808 \n\nExcitotoxicity and NMDA receptor-mediated \nacquired neuroprotection in human iPSC-derived \nbrain organoids\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .