AGE-RELATED EFFECTS OF TRIPHENYL PHOSPHITE-INDUCED DELAYED NEUROPATHYON CENTRAL VISUAL PATHWAYS IN THE EUROPEAN FERRET (MUSTELA-PUTORIUS-FURO)

The objective of this study was to investigate the relationship betwee n the maturation of visual system neurons and the onset of their susce ptibility to triphenyl phosphite (TPP)-induced delayed neurotoxicity i n the European ferret. We administered single subcutaneous doses of TP P (1184 mg/kg body wt) to 1- to 10-week-old ferret kits to assess the effects on connections and neurons of the developing lateral geniculat e thalamic nucleus (LGN) and primary visual cortex. Brains were proces sed with a modified Fink-Heimer silver-impregnation method. Axonal and terminal degeneration were first noted in the LGN of kits injected at 5 weeks of age. The severity of the degeneration increased in kits in jected at later ages and reached adult densities and configurations in ferrets injected at 10 weeks of age. Degenerating neuronal cell bodie s were also present in the LGN of kits injected at 7 weeks of age and older. In the visual cortex, axonal and terminal degeneration were con sistently present in kits injected at 8 weeks of age and attained adul t-like densities in kits injected at 10 weeks of age. Previous studies have reported that the ferret visual system appears to reach anatomic al maturity (as defined by mature LGN lamination patterns, the locatio n and density of axon terminals originating from neurons in the retina and LGN, and the migration and synaptic connections of cortical neuro ns) by 4-5 weeks of age. A temporal comparison of these normal develop mental data with the degeneration data obtained in the present study s uggests that immature neurons in the visual system of the ferret are n ot susceptible to TPP-induced delayed neurotoxicity but only become so after they have achieved some degree of maturity. Whether the LGN neu rons undergoing degeneration are directly affected by TPP or are showi ng a transneuronal response to loss of afferent input remains unresolv ed. (C) 1994 Society of Toxicology.