title: Excitotoxin-induced caspase-3 activation and microtubule disintegration in axons is inhibited by taxol.
abstract: BACKGROUND
  Axon degeneration, a key pathological event in many neurodegenerative diseases and injury, can be induced by somatodendritic excitotoxin exposure. It is currently unclear, however, whether excitotoxin-induced axon degeneration is mechanistically similar to Wallerian degeneration, which occurs following axon transection, but does not involve axonal caspase activation.
  
  
  RESULTS
  We have used mouse primary cortical neurons at 9 days in vitro, in a compartmented culture model that allows separation of the axon from the soma, to examine the pathological cascade of excitotoxin-induced axon degeneration. Excitotoxicity induced by chronic exposure to kainic acid, resulted in axonal fragmentation, which was associated with activation of caspase-3 in the axonal compartment. To examine the role of microtubules in these events, the microtubule-stabilizing agent, taxol, was added to either the axonal or somatodendritic compartment. Our results demonstrated that microtubule stabilization of axons resulted in a significant reduction in the number of fragmented axons following excitotoxin exposure. Interestingly, taxol exposure to either the somatodendritic or axonal compartment resulted in reduced caspase-3 activation in axons, suggesting that caspase activation is a downstream event of microtubule destabilization and involves signalling from the cell soma.
  
  
  CONCLUSIONS
  These data suggest that excitotoxin-induced axon degeneration shows some mechanistic differences to Wallerian degeneration, and that microtubule stabilization may assist in protecting nerve cells from excitotoxic effects.
authors.affiliation: Wicking Dementia Research and Education Centre, University of Tasmania, Private Bag 23, Hobart, Tasmania 7000, Australia. kingae@utas.edu.au.
authors.forename: Anna Elizabeth
authors.initials: AE
authors.lastname: King
authors.forename: Katherine Adriana
authors.initials: KA
authors.lastname: Southam
authors.forename: Justin
authors.initials: J
authors.lastname: Dittmann
authors.forename: James Clement
authors.initials: JC
authors.lastname: Vickers
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003599:Cytoskeleton / Q000187:drug effects / Q000502:physiology; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D014855:Wallerian Degeneration / Q000503:physiopathology
chemical_list: D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D018696:Neuroprotective Agents; C505409:Casp3 protein, mouse; D053148:Caspase 3; D017239:Paclitaxel; D007608:Kainic Acid