Attenuation of neurotoxicity following anoxia or glutamate receptor activation in EGF- and hippocampal extract-treated neuronal cultures.
Neurotoxicity following anoxia or glutamate receptor activation was studied in primary neuronal cultures grown in serum-free, chemically defined CDM R12 medium. Exposure to 1 mM KCN, 0.5 mM kainic acid and 0.5 mM N-methyl-D-aspartate led to progressive neuronal degeneration. This damage was quantified by measuring lactate dehydrogenase released in the culture medium. The toxic effects were observed early during the development of the neuronal culture (from 4 days in vitro on) and seemed to be neuron-specific since astrocyte cultures were not affected. Chronic treatment of the neuronal cultures with epidermal growth factor at 10 ng/ml and hippocampal extract at dil. 1/833 (w/v) induced morphological alterations, increased beta-adrenergic receptor coupled adenylate cyclase activity, increased level of total lactate dehydrogenase activity in the case of epidermal growth factor-treated cultures, and attenuation of lactate dehydrogenase release following exposure to KCN or glutamate receptor agonists. The alterations observed are probably due to the proliferation and differentiation of glial cells in these treated cultures. This suggests that glial cells protect neurons in vitro from degeneration induced by anoxia or glutamate receptor activation.
Pauwels
P J
PJ
Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.
van Assouw
H P
HP
Leysen
J E
JE
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000502:physiology; D006133:Growth Substances / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D002534:Hypoxia, Brain / Q000473:pathology; D007608:Kainic Acid / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D016202:N-Methylaspartate; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010100:Oxygen / Q000502:physiology*; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D006133:Growth Substances; D011943:Receptors, Adrenergic, beta; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D001224:Aspartic Acid; D004815:Epidermal Growth Factor; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D000262:Adenylyl Cyclases; D011190:Potassium Cyanide; D010100:Oxygen; D007608:Kainic Acid