Morphological evidence for increased protein synthesis in CNS neurons after soman exposure.
Fine structural changes in neurons of the dorsal hippocampus, caudate nucleus, supraoptic nucleus (SON), and ventral horn of the spinal cord of adult male or spayed female cats were studied after single and multiple doses (dose range 1.0-20.0 micrograms/kg sc) of the organophosphonate, pinacolyl methylphosphonofluoridate (soman). Increases in amounts of rough endoplasmic reticulum (rER) and polyribosomes, proliferation of Golgi complexes, as well as indentations of nuclear membranes occur after single and multiple exposures. The degree of change is dependent on dose, duration of exposure, and time of survival after exposure. The cell organelles affected are essential for protein synthesis and changes in their quantities are morphological indicators for changes in protein synthesis. The data presented in this study suggest an initial increase in protein synthesis after soman exposure, followed by early signs of degeneration. Soman (10 micrograms/kg iv) inhibition of cholinesterases of whole blood, spinal cord, and caudate nucleus of control and cats from which electrophysiological recordings of Renshaw cell field potentials were taken show significant differences. Moreover, while blood values are unmeasurable, spinal cord and caudate nucleus values are 42.21 and 53.6% those of controls at 30 min after injection and 63.41 and 50.75% those of controls after 240 min, respectively. No differences are noted between Renshaw cell field potentials after treatment and controls. Similarly, no changes in gross behavior are noted after 10 micrograms/kg sc. Yet, morphological signs of increases in protein synthesis are present. It is concluded that soman induces increased protein synthesis in many areas studied and that this increase is not dependent on inhibition of cholinesterase to a degree that affects gross behavior of evoked potentials from a CNS cholinergic-transmitting synapse--the motoneuron axon collateral and Renshaw cell (J. C. Eccles, P. Fatt, and K. Koketsu (1954), J. Physiol, 126, 524-562).
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002802:Cholinesterases / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011132:Polyribosomes / Q000187:drug effects; D012999:Soman / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects; D013495:Supraoptic Nucleus / Q000187:drug effects; D014317:Tritolyl Phosphates / Q000633:toxicity
D009419:Nerve Tissue Proteins; D014317:Tritolyl Phosphates; D012999:Soman; D002802:Cholinesterases; C025541:tri-o-cresyl phosphate