Astrocytes exert a pro-apoptotic effect on neurons in postnatal hippocampal cultures

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, in...

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Bibliographic Details
Published in:Neuroscience 2005, Vol.131 (2), p.349-358
Main Authors: Shute, A.A., Cormier, R.J., Moulder, K.L., Benz, A., Isenberg, K.E., Zorumski, C.F., Mennerick, S.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
apoptosis
Apoptosis - drug effects
Apoptosis - physiology
astrocyte
Astrocytes - cytology
Astrocytes - drug effects
Astrocytes - physiology
Biological and medical sciences
Ca 2+ current
Cell Survival - drug effects
Cell Survival - physiology
Cells, Cultured
Fundamental and applied biological sciences. Psychology
GABA
glutamate
Glutamic Acid - pharmacology
hippocampus
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - physiology
Nifedipine - pharmacology
Rats
Vertebrates: nervous system and sense organs
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Summary: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.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2004.11.025