Tissue-type plasminogen activator is not required for kainate-induced motoneuron death in vitro.
Spinal motoneurons are highly vulnerable to kainate both in vivo and in vitro. Tissue-type plasminogen activator (tPA) and plasmin have recently been shown to mediate kainate-induced neuronal death in the mouse hippocampus in vivo. The aim of the present study was to determine whether tPA also mediates the kainate-induced death of motoneurons in vitro. A motoneuron-enriched neuronal population was isolated from the ventral spinal cord of wild-type (WT) and tPA-deficient (tPA-/-) mouse embryos. WT and tPA-/- neurons were cultured on WT and tPA-/- spinal glial feeder layers, respectively. WT and tPA-/- co-cultures were morphologically indistinguishable. Expression of tPA in WT co-cultures was demonstrated using RT-PCR. WT and tPA-/- co-cultures were exposed to kainate for 24 h. The neurotoxic effect of kainate did not differ significantly between WT and tPA-/- cultures. The plasmin inhibitor alpha2-antiplasmin did not protect WT neurons against kainate-induced injury. These results indicate that the plasmin system is not a universal mediator of kainate-induced excitotoxicity.
Department of Neurology, University Hospital Gasthuisberg, Leuven, Belgium.
W
W
Vandenberghe
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L
Van Den Bosch
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W
Robberecht
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005341:Fibrinolysin / Q000502:physiology; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects*; D009457:Neuroglia / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018091:Receptors, AMPA / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D010959:Tissue Plasminogen Activator / Q000172:deficiency / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D012333:RNA, Messenger; D018091:Receptors, AMPA; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D007608:Kainic Acid