Intraocular tetrodotoxin reduces axonal transport and transcellular transfer of adenosine and other nucleosides in the visual system of goldfish.
Intraocular injection of tetrodotoxin (TTX) in goldfish, which abolishes physiological activity in the optic axons, decreased by up to about 30% the amount of radioactively labeled adenosine, uridine and guanosine (and their nucleotide derivatives) that was axonally transported in the optic nerve. The amount of labeled nucleoside that reached the optic tectum and became incorporated into RNA in the postsynaptic tectal neurons and glial cells was reduced by up to about 50%. There was no change, however, in the amount of transported nucleoside that became incorporated into RNA in the optic nerve glia. The TTX-induced changes were eliminated when axonal transport was blocked with vincristine, indicating that this change did not involve material moving along the nerve by diffusion. If the TTX injection was delayed until several hours after labeling of the transported materials, the transported labeled nucleoside in the nerve was reduced very little, but the RNA labeling in the tectum was reduced just as much as when TTX was given prior to labeling. This indicates that the labeling of the tectal cells was affected more by the level of activity in the pathway than by the amount of transported nucleoside reaching the optic nerve terminals. It appears likely, therefore, that the process most affected by the decrease in physiological activity is the release of nucleoside from the terminals of the presynaptic neurons or its uptake into postsynaptic tectal neurons and glia. The fact that physiological activity may modify the amount of axonally transported nucleosides made available for metabolism (including RNA synthesis) in postsynaptic neurons may provide an explanation for activity-linked neurotrophic effects.
D L
DL
Edwards
B
B
Grafstein
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D003530:Cyprinidae / Q000502:physiology*; D006054:Goldfish / Q000502:physiology*; D006151:Guanosine / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism*; D009900:Optic Nerve / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D013477:Superior Colliculi / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*; D014529:Uridine / Q000378:metabolism
D009705:Nucleosides; D006151:Guanosine; D013779:Tetrodotoxin; D012313:RNA; D000241:Adenosine; D014529:Uridine