Effects of dark-rearing on triphenyl phosphite-induced neuropathy in the visual system of the developing European ferret (Mustela putorius furo)

Results of a previous study in our lab (Tanaka et al., 1994) suggested that the onset of susceptibility to the organophosphorus compound triphenyl pho sphite (TPP) in the developing ferret visual system might be closely relate d to eye opening and the onset of light stimulation, in order to explore th is idea further, TPP was administered to ferret kits that had been raised f or varying periods of time in total darkness to assess whether a delay in t he onset of light stimulation to the visual system might also result in a d elay in its susceptibility to TPP. Ferret kits were raised from birth eithe r in total darkness or in open-sided sheds exposed to ambient light, inject ed subcutaneously with TPP (888 mg/kg body weight) at 5.5, 7.5, 9.5, or 21. 5 wk of age, euthanized, and perfused transcardially with a 10% formalin-sa line solution 4 d after injection. Brains were sectioned parasagittally at a thickness of 40 mu m and subsequently processed with the Fink-Heimer silv er impregnation technique to reveal the presence of degenerating axons and terminals, and with cresyl violet stain to delineate nuclear boundaries and fell soma morphology. Comparisons among degeneration patterns present in l ight-reared and dark-reared kits at the four ages examined revealed that th e time of onset, extent, and density of TPP-induced axonal and terminal deg eneration seen in the lateral geniculate nucleus and primary visual cortex did not differ significantly between light- and dark-reared groups, with th e possible exception of dark-reared kits exposed to TPP at 7.5 wk of age. I n addition, neurons in the primary visual cortex showed shrinkage and incre ased packing densities in kits exposed to TPP in both light and dark enviro nments, as well as in dark-reared noninjected kits. The results of this stu dy indicate that dark-rearing does not delay the onset or lessen the severi ty of TPP-induced axonal and terminal degeneration in the developing visual system of the ferret. Data suggest that light activation and stimulation o f the retinogeniculo-striatal visual pathway is not a necessary prerequisit e for the onset of visual system susceptibility to the axonopathic effects of triphenyl phosphite.