Enhanced mRNA expression of neurofilament subunits in the brain and spinal cord of diisopropyl phosphorofluoridate-treated hens.
Diisopropyl phosphorofluoridate (DFP) is an organophosphorus ester, and a single injection of this compound (1.7 mg/kg, s.c.) produces delayed neurotoxicity (OPIDN) in hens in 7-14 days. Clinically, the disease is marked by hindlimb ataxia followed by paralysis after some time. A characteristic feature of this neuropathy is axonal swelling in the initial stages and comparative dissolution of the accumulated material and degeneration of distal axons with disease progression. Axonal swelling consists of aggregated neurofilaments, microtubules, and proliferated smooth endoplasmic reticulum. We studied expression of neurofilament (NF) mRNAs in brain regions and spinal cord to elucidate their role in OPIDN. There was a 50-200% increase in NF transcripts in 24 hr after DFP administration. The NF-L mRNA level started falling after 1-5 days and came down to control level in susceptible brain regions (i.e. cerebellum and brainstem) and spinal cord, but not in cerebral cortex, which does not show degeneration of axons in OPIDN. Cerebral cortex exhibited elevated levels of both NF-L and NF-M transcripts in DFP-treated hens throughout the period of observation. The induction of NF messages is consistent with the previously reported effect on extension of neurites of human neuroblastoma cells in culture. The transient increase in NF messages in susceptible tissues either may be responsible for the delayed degeneration of axons in OPIDN or is the result of interruption of regulatory signal due to progressive degeneration of axons.
Gupta
R P
RP
Department of Pharmacology, Duke University Medical Center, Durham, NC 27708, USA.
Lin
W W
WW
Abou-Donia
M B
MB
D000818:Animals; D001921:Brain / Q000378:metabolism*; D001933:Brain Stem / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002645:Chickens; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D005260:Female; D007531:Isoflurophate / Q000494:pharmacology*; D016900:Neurofilament Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D013116:Spinal Cord / Q000378:metabolism*
D002800:Cholinesterase Inhibitors; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D007531:Isoflurophate