Long-term induction of Fos-related antigen-2 after methamphetamine-, methylenedioxymethamphetamine-, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine- and trimethyltin-induced brain injury.
A long-term induction of Fos-related antigens has been shown in neurons after brain injury, suggesting that Fos-related antigens are involved in enhancing the transcription of genes related to the process of regeneration and repair. In the present study, we report that levels of Fos-related antigen-2 are elevated in several models of chemically induced brain injury. Trimethyltin, which causes degeneration of neurons primarily in the hippocampus and other limbic regions, results in a five-fold induction of Fos-related antigen-2 immunoreactivity in neurons in the pyramidal and dentate layers of the hippocampus starting at seven days post-treatment and persisting for 60days. Methamphetamine and methylenedioxymethamphetamine, agents which cause degeneration of dopaminergic nerve terminals in the striatum of the mouse, cause an increase in Fos-related antigen-2 immunoreactivity which begins at three days post-treatment and returns to basal levels by days 5 and 15, respectively. Treatment with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine elevated levels of Fos-related antigen-2 in the mouse striatum at three days post-treatment. This abbreviated time-course of Fos-related antigen-2 induction is consistent with less severe insult (terminal damage) relative to trimethyltin (cell death), but induction occurs during the period of regeneration and repair in both models. Dexfenfluramine, a non-neurotoxic amphetamine, does not induce Fos-related antigen-2 expression. Decreasing core temperature of the mouse, which blocks amphetamine-induced neurotoxicity, also blocks Fos-related antigen-2 induction. In summary, Fos-related antigen-2 is induced in models of both cell death and terminal degeneration, suggesting that this transcription factor may serve as a universal signal transduction molecule involved in the regulation of genes related to regeneration and repair in the CNS.
Pennypacker
K R
KR
University of South Florida, College of Medicine, Department of Pharmacology and Therapeutics, Tampa, FL 33612, USA. kpennypa@hsc.usf.edu
Yang
X
X
Gordon
M N
MN
Benkovic
S
S
Miller
D
D
O'Callaghan
J P
JP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015259:Dopamine Agents; D051921:Fos-Related Antigen-2; D007150:Immunohistochemistry; D008297:Male; D008694:Methamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014298:Trimethyltin Compounds
D004268:DNA-Binding Proteins; D015259:Dopamine Agents; D051921:Fos-Related Antigen-2; C497874:Fosl2 protein, rat; D014157:Transcription Factors; D014298:Trimethyltin Compounds; C046488:trimethyltin; D008694:Methamphetamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D018817:N-Methyl-3,4-methylenedioxyamphetamine