Altered expression of transcripts for alpha-tubulin and an unidentified gene in the spinal cord of phenyl saligenin phosphate treated hens (Gallus gallus).
Phenyl saligenin phosphate (PSP) induces a central-peripheral distal axonopathy in domestic fowl that develops 7-21 days after a single exposure. Neurotoxic esterase (NTE) is the initial molecular target for this neurotoxicity. PSP has to covalently bind to NTE and chemically "age" for induction of axonopathy. It was hypothesized that exposure to PSP results in early changes in spinal cord gene expression that do not occur with phenylmethylsulfonyl fluoride, a non-neuropathic compound that also inhibits NTE, or DMSO controls. Targeted display was used to screen approximately 15,000 gel bands. Three candidate genes were identified, but only the transcript designated P1 showed decreased expression following PSP exposure (2 mg/kg i.m.) in subsequent Northern blot and in situ hybridization experiments in samples taken <48 h after exposure. Additional experiments revealed that a approximately 2.5 kb alpha-tubulin transcript had decreased expression at 12-48 h after PSP exposure, with maximum change at 48 h (33%, p = 0.0479). A approximately 4.5 kb alpha-tubulin transcript had increased expression at 12 h (38%, p = 0.0125) and decreased expression at 48 h (28%, p = 0.0576). In situ hybridization on spinal cord revealed neuronal expression of P1 and alpha-tubulin transcripts. Decreased expression of transcripts for P1 and alpha-tubulin was present at 12 and 48 h, respectively. This decrease occurred in all neurons, not just those whose axons degenerate. Results suggest that (1) in PSP-induced OPIDN (organophosphorus-induced delayed neurotoxicity) some gene transcript expression changes are associated with initiation of axonopathy, and (2) PSP modulates spinal cord gene expression in neuronal types that do not undergo axonal degeneration.
Fox
Jonathan H
JH
Laboratory for Neurotoxicity Studies, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA 24061, USA.
Jortner
Bernard S
BS
Barber
David
D
Ehrich
Marion F
MF
D000818:Animals; D001369:Axons / Q000187:drug effects; D015152:Blotting, Northern; D002645:Chickens; D003001:Cloning, Molecular; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D017403:In Situ Hybridization; D007273:Injections, Intramuscular; D008161:Lumbosacral Region; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic; D014404:Tubulin / Q000235:genetics*
D009943:Organophosphorus Compounds; D014404:Tubulin; C046357:phenylsaligenin cyclic phosphate