title: Astrocytes exert a pro-apoptotic effect on neurons in postnatal hippocampal cultures.
abstract: We investigated conditions that promote basal and activity-dependent neuronal apoptosis in postnatal rat hippocampal cultures. Low-density mixed cultures of astrocytes and neurons exhibited lower sensitivity than high-density cultures to basal neuronal death and activity-sensitive neuronal death, induced with glutamate receptor blockers, sodium channel blockers, or calcium channel blockers. Although elevations of [Ca(2+)](i) protect neurons from apoptosis, low-density microcultures and mass cultures exhibited only minor differences in resting [Ca(2+)](i) and Ca(2+) current density, suggesting that these variables are unlikely to explain differences in susceptibility. Astrocytes, rather than neurons, were implicated in the neuronal loss. Several candidate molecules implicated in other astrocyte-dependent neurotoxicity models were excluded, but heat inactivation experiments suggested that a heat-labile factor is critically involved. In sum, our results suggest the surprising result that astrocytes can be negative modulators of neuronal survival during development and when the immature nervous system is challenged with drugs that dampen electrical excitability.
authors.affiliation: Departments of Psychiatry and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8134, St. Louis, MO 63110, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Shute
authors.forename: R J
authors.initials: RJ
authors.lastname: Cormier
authors.forename: K L
authors.initials: KL
authors.lastname: Moulder
authors.forename: A
authors.initials: A
authors.lastname: Benz
authors.forename: K E
authors.initials: KE
authors.lastname: Isenberg
authors.forename: C F
authors.initials: CF
authors.lastname: Zorumski
authors.forename: S
authors.initials: S
authors.lastname: Mennerick
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats
chemical_list: D018698:Glutamic Acid; D009543:Nifedipine