Absence of the GluR2 receptor sensitizes mouse sympathetic neurons to nerve growth factor deprivation.

Over-activation of glutamate receptors is implicated in neurodegeneration. Using mice with a deletion in the GluR2 gene, we studied the sensitivity of sympathetic neurons to reduced levels of nerve growth factor (NGF), which can cause neuronal cell death. Under standard culture conditions of 50 ng/ml NGF, neurons from the superior cervical ganglion survived and grew equally well compared with wild type controls. However, the subsequent reduction of NGF levels caused significantly poorer survival among mutant neurons by 48 h, at 44+/-13% of control at 10 ng/ml NGF, and dropping further to 14+/-6% at 0.05 ng/ml NGF. These results suggest that the absence of GluR2 impairs the ability of these NGF-sensitive neurons to survive under limiting amounts of this neurotrophic factor.