Kainic acid induces apoptosis in neurons

• Published in: Neuroscience Vol. 75; no. 4; pp. 1047 - 1055
• 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 01-12-1996; Elsevier
• Subjects: Ageing, cell death; Animals; Animals, Newborn; Apoptosis - drug effects; Biological and medical sciences; cell death; Cell Nucleus - drug effects; Cell Nucleus - ultrastructure; Cell physiology; Cell Survival - drug effects; Cells, Cultured; cerebellar granule cells; Cerebellum - cytology; Cerebellum - physiology; Dizocilpine Maleate - pharmacology; DNA - analysis; Excitatory Amino Acid Antagonists - pharmacology; excitoxicity; Fundamental and applied biological sciences. Psychology; Kainic Acid - pharmacology; Kinetics; Methionine - metabolism; Molecular and cellular biology; Nerve Tissue Proteins - biosynthesis; Neurons - cytology; Neurons - drug effects; Neurons - physiology; Quinoxalines - pharmacology; Rats; Rats, Sprague-Dawley; Time Factors; BSA, bovine serum albumin; DNQX, 6,7-dinitroquinoxaline-2,3-dione; cell death; EDTA, ethylenediaminetetra-acetate; low K +, low potassium; AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; HEPES, N-2-hydroxyethylpiperazine- N′-2-ethanesulphonic acid; MK-801, dizocilpine maleate; excitoxicity; TBS, Tris-buffered saline; CGC, cerebellar granule cell; ALS, amyotrophic lateral sclerosis; ATA, auritricarboxylic acid; HBSS, Hanks balanced salt solution; cerebellar granule cells; SDS, sodium dodecyl sulphate; NMDA, N-methyl- d-aspartate; Locke's, sodium-free Locke's; Cerebellum; Granule neuron; Cell death; Central nervous system; Neurotoxin; Neurotransmitter; Excitatory aminoacid; Glutamate receptor; In vitro; Brain (vertebrata); Apoptosis; Kainate receptor
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/0306-4522(96)00326-0

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 kainic acid neurotoxicity using cerebellar granule cell neurons
in vitro and we sought to determine the mechanism of kainic acid-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 kainic acid (100
μM). Aurintricarboxylic acid protected cerebellar granule cells from kainic acid-induced death. While the morphological and biochemical features of neuronal death induced by kainic acid resembled low K
+-induced apoptosis in cerebellar granule cells, the time interval from the institution of the death promoting condition to neuronal death was shorter with kainic acid and did not require new protein or RNA synthesis.
These results demonstrate that kainic acid receptor activation can induce transcription-independent apoptosis in neurons. This
in vitro model should be useful in identifying the intracellular pathways that link kainic acid receptor activation with apoptosis.