Selective axonal and terminal degeneration in the chicken brainstem and cerebellum following exposure to bis(1-methylethyl)phosphorofluoridate (DFP).
Utilizing a variation of the Fink-Heimer method, we examined the extent and location of axonal and terminal degeneration within the chicken cervical spinal cord, brainstem and cerebellum resulting from a single subcutaneous dose of bis(1-methylethyl)phosphorofluoridate (DFP). The effects of DFP on the activities of whole-brain neuropathy target esterase (NTE) and cholinesterase (ChE) were also assessed as were the development and severity of clinical signs characteristic of organophosphorus-induced delayed neuropathy (OPIDN). Both whole brain NTE and ChE activities were maximally inhibited during the first 24 h post-exposure, showing gradual recovery over a period of 3 weeks. OPIDN clinical signs were not observed at 7 days post-DFP but progressed to severe ataxia by day 14 and paralysis by day 21. There was a relative absence of degeneration at 7 days, a dramatic increase in degeneration density at 14 days, and high density degeneration at both 21 and 28 days. Cervical spinal and medullary tracts containing axonal degeneration included the fasciculus gracilis, dorsal and ventral spinocerebellar tracts, spinal lemniscus, and the intramedullary portions of the glossopharyngeal and vagus nerves. Brainstem nuclei containing terminal degeneration included the lateral cervical, gracile-cuneate, external cuneate, and inferior olivary nuclei, the nucleus tractus solitarius, and the lateral and paragigantocellular lateral reticular nuclei. Mossy fiber degeneration was also present in cerebellar folia I-Vb. These results show that exposure to DFP causes axonal and terminal degeneration in ascending spinal tracts, brainstem nuclei and cerebellar folia associated with the transmission of somatic and visceral sensory information.
Tanaka
D
D
Department of Anatomy, Michigan State University, East Lansing 48824.
Bursian
S J
SJ
Lehning
E
E
D000818:Animals; D001259:Ataxia / Q000139:chemically induced / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D001933:Brain Stem / Q000187:drug effects / Q000473:pathology*; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000473:pathology*; D002645:Chickens; D002802:Cholinesterases / Q000378:metabolism; D007531:Isoflurophate / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D012016:Reference Values
D009498:Neurotoxins; D007531:Isoflurophate; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D002802:Cholinesterases