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EnglishCultured granule cells grown in serum-containing medium with a ''low K+'' concentration (10 mM) underwent apoptosis after maturation for 5 days in vitro (5 DIV), a time that coincides with the developmental decline in the activity of metabotropic glutamate receptors (mGluRs) coupled to polyphosphoinositide hydrolysis. The mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) prevented the development of low K+-induced apoptosis and the presence of the drug was critical at 6 and 7 DIV, i.e., after the drop of mGluR activity. The neuroprotective action of 1S,3R-ACPD was prevented by the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) and was mimicked by N-methyl-D-aspartate or carbamylcholine but not by agonists of the mGluR subtypes negatively linked to adenylyl cyclase. In cultures treated either with Li+-which reduced polyphosphoinositide response to concentrations of glutamate (5 mu M) that approximate those physiologically present in the incubation medium-or MCPG, the development of low K+-induced apoptosis already occurred at 4 DIV. Thus, the activation of mGluRs coupled to polyphosphoinositide hydrolysis by endogenous glutamate could contribute to protect cultured granule cells against apoptosis during early stages of maturation.
| Titolo: | Activation of metabotropic glutamate receptors prevents neuronal apoptosis in culture |
| Autori interni: | |
| Data di pubblicazione: | 1995 |
| Rivista: | |
| Handle: | http://hdl.handle.net/20.500.11769/19948 |
| Appare nelle tipologie: | 1.1 Articolo in rivista |
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http://hdl.handle.net/20.500.11769/19948
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