Nerve cell death induced in vivo by kainic acid and quinolinic acid does not involve apoptosis.
We investigated whether in vivo excitotoxicity was mediated by a mechanism of programmed cell death called apoptosis. Neurotoxic doses of kainic acid (1.2 nmol) and quinolinic acid (120 nmol) were unilaterally injected in the dorsal hippocampus of anesthetized rats. Eight or 16 h later the animals were killed and DNA was extracted from the injected hippocampi. DNA from mouse thymocytes exposed to methylprednisolone (10(-5) M for 6 h at 37 degrees C) was used as a positive control of apoptotic cells. No typical 'ladder' of DNA fragments (multimers of approximately 200 Kb) which characterizes apoptosis was seen in hippocampal cells after toxic doses of kainic or quinolinic acid, as assessed by agarose gel electrophoresis. This suggests that hippocampal nerve cell death induced in vivo by the excitotoxins is not mediated by apoptosis.
Ignatowicz
E
E
Laboratory of Cancer Chemotherapy and Neuropharmacology, Istituto di Ricerche Farmacologiche 'Mario Negri', Milano, Italy.
Vezzani
A M
AM
Rizzi
M
M
D'Incalci
M
M
D000818:Animals; D002118:Calcium / Q000502:physiology; D016923:Cell Death / Q000187:drug effects; D004247:DNA / Q000032:analysis; D004587:Electrophoresis, Agar Gel; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D011805:Quinolinic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D004247:DNA; D017378:Quinolinic Acid; D007608:Kainic Acid; D002118:Calcium; D008775:Methylprednisolone