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 oligodeoxynucleotide (ASO) treatment against excitatory amino acid (EAA)-induced neurotoxicity in rat hippocampal neurons. Glutamate (in vitro) or NMDA (in vivo) produced significant neuronal degeneration. Neuroprotection produced by 30 min or 4 h pretreatment with c-fos ASO in cultured hippocampal neurons was dose-dependent. In vivo, bilateral intrahippocampal injections of c-fos ASO (0.025 nmol/site) was neuroprotective 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 neuroprotective effect of c-fos ASO against EAA-induced neuronal injury supporting a causative role of c-fos expression in EAA neurotoxicity.
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Department of Neuropharmacology and Molecular Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA.
Tortella
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Ved
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Garcia
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Dave
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D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D016376:Oligonucleotides, Antisense; D016760:Proto-Oncogene Proteins c-fos; D016202:N-Methylaspartate