Presynaptic terminal loss from alpha-motoneurones following the retrograde axonal transport of diphtheria toxin.
Intercostal motoneurones intoxicated following intraneural injection of diphtheria toxin exhibited a progressive dilatation and fragmentation of Nissl body rough endoplasmic reticulum (rER), coupled with two different forms of presynaptic terminal response. Firstly, terminal dysjunction without prior degeneration, and secondly, Wallerian-type degeneration. Dysjunction was attributed to a toxin-related failure by the motoneurones to maintain postsynaptic site structure. Degeneration was considered to arise from toxicity in presynaptic neurones, either neighbouring motoneurones or local interneurones. Morphometry revealed that by 8 days, intoxicated motoneurones exhibited a 33% loss in terminal frequency, a 15% loss in residual presynaptic membrane, and a 43% loss in overall presynaptic input. The concomitant loss of synaptic sites was greater that the overall loss of presynaptic membrane, indicating a toxin-related deficiency of the maintenance of postsynaptic sites. Analyses of the relationship between changes in terminal numbers and the development of Nissl body abnormality in the postsynaptic motoneurone identified three groups of motoneurones: (i) those with normal presynaptic input and normal neuronal Nissl body rER; (ii) those showing a dramatic loss of presynaptic input and a marked dilatation and fragmentation of Nissl bodies; and (iii) neurones exhibiting a maintained or further loss of presynaptic input coupled with extreme dilatation and fragmentation of Nissl body rER with loss of Nissl body structure. These changes are discussed in context with the known molecular action of diphtheria toxin.
Pullen
A H
AH
Sobell Department of Neurophysiology, Institute of Neurology, Queen Square, London, UK.
D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D002415:Cats; D004167:Diphtheria Toxin / Q000633:toxicity*; D004721:Endoplasmic Reticulum / Q000648:ultrastructure; D009046:Motor Neurons / Q000187:drug effects / Q000648:ultrastructure*; D009411:Nerve Endings / Q000187:drug effects / Q000648:ultrastructure*; D009457:Neuroglia / Q000187:drug effects / Q000648:ultrastructure; D009562:Nissl Bodies / Q000648:ultrastructure; D013116:Spinal Cord / Q000187:drug effects / Q000648:ultrastructure; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure*; D014855:Wallerian Degeneration / Q000187:drug effects
D004167:Diphtheria Toxin