Early differential induction of c-jun in the central nervous system of hens treated with diisopropylphosphorofluoridate (DFP)

Diisopropyl phosphorofluoridate (DFP) produces organophosphorus-ester induc ed delayed neurotoxicity (OPIDN) in the hen, human and other sensitive spec ies. We studied the effect of a single dose of DFP (1.7 mg/kg/sc) on the ex pression of c-jun, which is one of the heterodimerizing ITFs (Inducible Tra nscriptional Factors) of the AP-I family. The hens were sacrificed at diffe rent time points ie 0.25,.0.50, 1 and 2 hrs. Total RNA was extracted from t he following brain regions: cerebrum, cerebellum, brainstem, midbrain and a s well as spinal cord. Northern blots prepared using standard protocols wer e hybridized with c-jun as well as b-actin and 18S RNA cDNA (control) probe s. The results indicate differential regulation of c-jun levels which may b e due to the activation of both cholinergic and non-cholinergic pathways of CNS, besides changing roles of c-jun (as mediator of degeneration or regen eration) depending on heterodimerization with other ITFs. In the highly sus ceptible tissues like brainstem and spinal cord c-jun transcript levels inc reased at 15 minutes and continued to increase gradually till it reached th e maximum at 2 hrs. Overall spinal cord showed the maximum levels of c-jun induction (207%) at 2 hrs time point of all the CNS tissues. The enhancemen t of cholinergic transmission by the inhibition of cholinestrase may be res ponsible for the gradual increase mediated by neural and vascular factors. In contrast, less susceptible tissue, cerebellum showed almost immediate in duction to high level of (179%) at 15 minutes and the levels stayed more or less the same until it peaked to 185% at 2 hrs. Relatively low abundance o f cholinergic neurons and high number of sensitized specialized cell types like Bergman glia and Purkinje cells may be responsible for the immediate h igher induction. Non-susceptible tissue cerebrum did not show any changes i n the c-jun levels, In midbrain the induction pattern was very similar to t hat of brainstem. This differential induction pattern of c-jun encomposing the differences in the quantity and time course was directly proportionate to the degree of susceptibility and cellular heterogeneity of different reg ions of CNS. The significant increase in c-jun levels along with our earlie r observation on the increased c-fos levels indicate that AP-1 family of ge nes may be one of the IEGs involved in the long term changes which eventual ly lead to OPIDN.