NEUROPROTECTIVE ROLE OF C-FOS ANTISENSE OLIGONUCLEOTIDE - IN-VITRO AND IN-VIVO STUDIES

WE investigated the dose-response and time-course of c-fos antisense o ligodeoxynucleotide (ASO) treatment against excitatory amino acid (EAA )-induced neurotoxicity in rat hippocampal neurons. Glutamate (in vitr o) or NMDA (in vivo) produced significant neuronal degeneration. Neuro protection produced by 30 min or 4 h pretreatment with c-fos ASO in cu ltured hippocampal neurons was dose-dependent. In vivo, bilateral intr ahippocampal injections of c-fos ASO (0.025 nmol/site) was neuroprotec tive when administered 30 min before or after NMDA treatment. However, 4 h pretreatment was ineffective. A higher dose (0.125 nmol) of c-fos ASO was neurotoxic and failed to afford neuroprotection regardless of the treatment schedule. Collectively, these results demonstrate a neu roprotective effect of c-fos ASO against EAA-induced neuronal injury s upporting a causative role of c-fos expression in EAA neurotoxicity.