C-fos mRNA induction in the central and peripheral nervous systems of diisopropyl phosphorofluoridate (DFP)-treated hens.
A single dose of diisopropyl phosphorofluoridate (DFP), an organophosphorus ester, produces delayed neurotoxicity (OPIDN) in hen. DFP produces mild ataxia in hens in 7-14 days, which develops into severe ataxia or paralysis as the disease progresses. Since, OPIDN is associated with alteration in the expression of several proteins (e.g., Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) alpha-subunit, tau, tubulin, neurofilament (NF) protein, vimentin, GFAP) as well as their mRNAs (e.g., NF, CaM kinase II alpha-subunit), we determined the effect of a single dose of DFP on the expression of one of the best known immediate-early gene (IEG), c-fos. C-fos expression was measured by Northern hybridization in cerebrum, cerebellum, brainstem, midbrain, spinal cord, and the sciatic nerves of hens at 0.5 hr, 1 hr, 2 hr, 1 day, 5 days, 10 days, and 20 days after a single 1.7 mg/kg, sc. injection of DFP. All the tissues (cerebrum, 52%; cerebellum, 55%; brainstem, 49%; midbrain, 23%; spinal cord, 80%; sciatic nerve, 157%) showed significant increase in c-fos expression in 30 min and this elevated level persisted at least up to 2 hr. Expressions of beta-actin mRNA and 18S RNA were used as internal controls. The significant increase in c-fos expression in DFP-treated hens suggests that c-fos may be one of the IEGs involved in the development of OPIDN.
Gupta
R P
RP
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27708, USA.
Damodaran
T V
TV
Abou-Donia
M B
MB
D000818:Animals; D015152:Blotting, Northern; D001933:Brain Stem / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002645:Chickens; D066298:In Vitro Techniques; D007531:Isoflurophate / Q000633:toxicity*; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D009928:Organ Specificity; D017933:Peripheral Nervous System / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012584:Sciatic Nerve / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D007531:Isoflurophate