Changes in hippocampal gene expression after neuroprotective activation of group I metabotropic glutamate receptors

Stimulation of group I metabotropic glutamate receptors (mGluRs) has been shown to protect against N-methyl-D-aspartate receptor-mediated cell death, but the underlying cellular mechanism is unknown. Using cDNA microarrays we have now compared gene expressions in organotypic hippocampal slice cultures after neuroprotective activation of group I mGluRs with (S)-3,5-dihydroxyphenylglycine (DHPG; 10 microM, 2 h) with untreated control cultures. Total RNA was extracted from the cultures immediately after the neuroprotective treatment, reverse transcribed to cDNA with incorporation of [32]P-dCTP, and then hybridized to the arrays. Of a total of 1128 genes on the Neuroarray, 33 genes displayed significant changes in expression after DHPG-treatment (six up- and 27 downregulated). These genes have been associated with regulation of synaptic excitation, inflammation, cell adhesion, cell death, and transcription. The small GTPase RAB5B associated with endocytosis emerged as a primary candidate gene for neuroprotection, and its expression was confirmed by Western blot analysis and real time polymerase chain reaction. By providing insight into genes involved in neuroprotection these data may help to identify novel therapeutic targets.