I have this question just out of curiosity. I read a couple of publications in which a saporin-conjugate is used to kill a specific neuron population, for example GABAergic neurons by stereotaxic injection of antiGAT-1-sap into the brain region of interest.
I guess the specificity of saporin-conjugates mostly are determined by specific receptor-ligand binding. This also means saporin can enter the cell or subcellular structure where this binding present. In the example mentioned above, is it also possible that antiGAT-1-sap kills the passing fibers/axons of long-range projection neurons that also GAT1 positive?
Let me know what you think, especially for those have employed a saporin-based methods for brain lesions. Thanks a lot! :)
Dear Jiahao, your idea is interesting. But, it is difficult to help you. Please evaluate carefully the paper in the attachment. May be you will find a way...
Vladimir
Dear Vladimir,
It is a stimulating article, thank you. "Unmodified saporin cannot enter cells but at high, micromolar concentrations it can trigger apoptosis due to background endocytosis."
Considering the very active vesicle recycling at synapses, the axonal protein synthesis and axoplasmic transport, it's then quite likely saporin can enter the axon, even being transported back to distal cell body.
It is better if we can have some input from who actually make lesion of neurons by toxins (i.e.Tetanus toxin, botulinum toxin). Probably, the concentration of toxin, the survival time are among the critical factors for a local lesion.
Best,
Jiahao
Dear Jiahao! I am glad that you are trying to find a way. All the best. Vladimir
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