Related Experiment Videos
Neuronal sensitivity to tetanus toxin requires gangliosides
L C Williamson1, K E Bateman, J C Clifford
1Laboratory of Developmental Neurobiology, NICHHD, National Institutes of Health, Bethesda, Maryland 20892-4480, USA.
The Journal of Biological Chemistry
|August 24, 1999
Summary
Tetanus toxin causes paralysis by blocking neurotransmitter release. Gangliosides are essential receptors for tetanus toxin, as blocking their synthesis prevents toxin binding and action in neurons.
Area of Science:
- Neuroscience
- Molecular Biology
- Toxicology
Background:
- Tetanus toxin induces spastic paralysis by inhibiting neurotransmitter release in the spinal cord.
- The precise role of di- and trisialogangliosides as functional receptors for tetanus toxin is not fully understood.
Purpose of the Study:
- To investigate the role of gangliosides as tetanus toxin receptors.
- To determine if inhibiting ganglioside synthesis affects tetanus toxin binding and neurotoxicity.
Main Methods:
- Mouse spinal cord neurons were cultured with fumonisin B(1), a ganglioside synthesis inhibitor.
- Toxin binding was assessed using toxin-horseradish peroxidase conjugates and immunofluorescence.
- Neurotransmitter release and synaptic function were measured in treated and untreated cultures.
Main Results:
- Fumonisin B(1) treatment inhibited ganglioside synthesis by over 90% but preserved neuronal morphology.
- Tetanus toxin failed to bind to neurons lacking gangliosides.
- Tetanus toxin did not block neurotransmitter release or impair synaptic function in treated cultures.
- Restoring gangliosides to treated cultures re-established tetanus toxin binding and neurotoxicity.
Conclusions:
- Gangliosides are crucial components of the receptor mechanism for tetanus toxin.
- Inhibiting ganglioside synthesis protects neurons from tetanus toxin-induced synaptic blockade.