Kainate induces apoptosis in neurons

• Published in: Neuroscience Vol. 74; no. 3; pp. 675 - 683
• Main Authors: Simonian, N.A, Getz, R.L, Leveque, J.C, Konradi, C, Coyle, J.T
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-10-1996; Elsevier
• Subjects: Animals; Anisomycin - pharmacology; Apoptosis; Aurintricarboxylic Acid - pharmacology; Biological and medical sciences; cell death; Cell Nucleus - drug effects; Cell Nucleus - ultrastructure; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; cerebellar granule cells; Cerebellum - cytology; Cerebellum - physiology; Cycloheximide - pharmacology; Dactinomycin - pharmacology; DNA - analysis; Electrophoresis, Agar Gel; excitotoxicity; Fundamental and applied biological sciences. Psychology; Kainic Acid - toxicity; Kinetics; Nerve Degeneration - drug effects; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Neurotoxins - toxicity; Rats; Rats, Sprague-Dawley; Vertebrates: nervous system and sense organs; DNQX, 6,7-dinitroquinoxaline-2,3-dione; cell death; EDTA, ethylenediaminetetra-acetate; HEPES, N-2-hydroxyethylpiperazine- N′-ethanesulfonic acid; KA, kainate; MK-801, dizocilpine maleate; ATA, aurintricarboxylic acid; CGC, cerebellar granule cell; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate; HBSS, Hank's balanced salt solution; cerebellar granule cells; excitotoxicity; NMDA, N-methyl- d-aspartate; Cerebellum; Vertebrata; Mammalia; Granule neuron; Rat; Cell death; Toxicity; Rodentia; Central nervous system; Glutamate receptor; Brain (vertebrata); Apoptosis
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(96)00141-8

Growing evidence suggests that non-
N-methyl-
d-aspartate receptor activation may contribute to neuronal death in both acute and chronic neurological diseases. The intracellular processes that mediate this form of neuronal death are poorly understood. We have previously characterized a model of kainate neurotoxicity using cerebellar granule cell neurons
in vitro and we sought to determine the mechanism of kainate-induced neuronal degeneration. We found DNA laddering by agarose gel electrophoresis, cellular DNA fragmentation by
in situ end labeling of DNA, and chromatin condensation using a fluorescent DNA intercalating dye, in cerebellar granule cells following exposure to kainate (100
μM). Aurintricarboxylic acid protected cerebellar granule cells from kainate-induced death. While the morphological and biochemical features of neuronal death induced by kainate resembled low-K
+-induced apoptosis in cerebellar granule cells, the time interval from the institution of the death-promoting condition to neuronal death was briefer with kainate and did not require new protein or RNA synthesis.
These results demonstrate that kainate receptor activation can induce transcription-independent apoptosis in neurons. This
in vitro model should be useful in identifying the intracellular pathways that link kainate receptor activation with apoptosis.