Alterations in levels of mRNAs coding for glial fibrillary acidic protein (GFAP) and vimentin genes in the central nervous system of hens treated with diisopropyl phosphorofluoridate (DFP).
Diisopropyl phophorofluoridate (DFP) produces organophosphorus-ester induced delayed neurotoxicity (OPIDN) in the hen, human and other sensitive species. We studied the effect of DFP admimistration (1.7 mg/kg/s.c.) on the expression of Intermediate Filament (IF) proteins: Glial Fibrillary Acidic Protein (GFAP) and vimentin which are known indicators of neurotoxicity and astroglial pathology. The hens were sacrificed at different time points i.e. 1,2,5,10 and 20 days. Total RNA was extracted from the following brain regions: cerebrum, cerebellum, and brainstem as well as spinal cord. Northern blots prepared using standard protocols were hybridized with GFAP and vimentin as well as beta-actin and 18S RNA cDNA (controls) probes. The results indicate a differential/spatial/temporal regulation of GFAP and vimentin levels which may be due to the result of disruption of glial-neuronal network. The GFAP transcript levels reached near control levels (88% and 95%) at 20 days post DFP treatment after an initial down-regulation (60% and 73%) in highly susceptible tissues like spinal cord and brainstem respectively. However vimentin transcript levels remained down-regulated (61% and 53%) at 20 days after an early reduced levels(47% and 55%) for spinal cord and brainstem respectively. This may be due to the astroglial pathology resulting in neuronal alterations or vice-versa. In cerebellum (less susceptile tissue) GFAP levels were moderately down-regulated at 1,2 and 5 days and reached near control values at 10 and 20 days. Vimentin was rapidly reinduced (128%) in cerebellum at 5 days and remained at the same level at 10 days and then returned to control values at 20 days after an initial down-regulation at 1 and 2 days. Thus these alterations were less drastic in cerebellum as indicated by initial susceptibility followed by rapid recovery. On the other hand both GFAP and vimentin levels were upregulated from 2 days onwards in the non-susceptible tissue cerebrum, implying protective mechanisms from the beginning. Hence the DFP induced astroglial pathology as indicated by the complex expression profile of GFAP and vimentin mRNA levels may be playing an important role in the delayed degeneration of axons or is the result of progressive degeneration of axons in OPIDN.
Damodaran
T V
TV
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27708, USA.
Abou-Donia
M B
MB
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002645:Chickens; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D007531:Isoflurophate / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics*; D014746:Vimentin / Q000235:genetics*
D005904:Glial Fibrillary Acidic Protein; D012333:RNA, Messenger; D014746:Vimentin; D007531:Isoflurophate