Cultured 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.

Activation of metabotropic glutamate receptors prevents neuronal apoptosis in culture

COPANI, Agata Graziella;BARRESI, VINCENZA;CONDORELLI, Daniele Filippo;
1995-01-01

Abstract

Cultured 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.
Apoptosis,; Cerebellar granule cells, ; Metabotropic glutamate receptors
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/19948
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