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

• Published in: Neuroscience 2000-01, Vol.101 (4), p.913-919
• Main Authors: Pennypacker, K.R, Yang, X, Gordon, M.N, Benkovic, S, Miller, D, O’Callaghan, J.P
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; AP-1; Biological and medical sciences; Brain Diseases - chemically induced; Brain Diseases - metabolism; Development. Senescence. Regeneration. Transplantation; DNA-Binding Proteins - metabolism; Dopamine Agents; Fos-Related Antigen-2; Fundamental and applied biological sciences. Psychology; gene regulation; glial fibrillary acidic protein; Immunohistochemistry; Male; Methamphetamine; methylenedioxymethamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; neuronal regeneration; Rats; Rats, Sprague-Dawley; terminal degeneration; Time Factors; transcription factor; Transcription Factors - metabolism; trimethyltin; Trimethyltin Compounds; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(00)00381-X

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 60 days. 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.