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Morphological evidence for increased protein synthesis in CNS neurons after soman exposure
Abstract:
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).
Insights
Exposure to soman, an organophosphonate, increases neuronal protein synthesis in cats, indicated by changes in organelles essential for protein production. This effect occurs even without significant cholinesterase inhibition impacting behavior or nerve signals.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Organophosphonates like soman are potent neurotoxins.
- Understanding soman's cellular effects is crucial for developing countermeasures.
- Previous research has focused on cholinesterase inhibition, but cellular responses require further investigation.
Purpose of the Study:
- To investigate the fine structural changes in feline neurons following soman exposure.
- To correlate these morphological changes with protein synthesis and cholinesterase activity.
- To determine if soman-induced protein synthesis is linked to behavioral or electrophysiological changes.
Main Methods:
- Adult cats (male and spayed female) were administered single and multiple doses of soman (1.0-20.0 µg/kg).
- Ultrastructural analysis of neurons in the dorsal hippocampus, caudate nucleus, supraoptic nucleus, and spinal cord ventral horn was performed.
- Cholinesterase activity in blood, spinal cord, and caudate nucleus was measured at various time points post-exposure.
- Electrophysiological recordings of Renshaw cell field potentials were conducted.
Main Results:
- Soman exposure led to increased rough endoplasmic reticulum, polyribosomes, and Golgi complexes, indicating enhanced protein synthesis.
- Nuclear membrane indentations were also observed.
- Cholinesterase inhibition was dose- and time-dependent, but significant behavioral or electrophysiological changes were not noted at the studied dose.
- Morphological signs of increased protein synthesis were present even when cholinesterase inhibition did not affect gross behavior or evoked potentials.
Conclusions:
- Soman induces increased protein synthesis in various feline neuronal populations.
- This increase in protein synthesis is not directly dependent on cholinesterase inhibition to a level affecting gross behavior or CNS synaptic transmission.
- Morphological alterations serve as early indicators of soman's impact on neuronal function.