Cell proliferation in the brains of NMDAR NR1 transgenic mice

We have used genetically engineered NMDA receptor NR1+/- mice in which the gene for the NR1 subunit was modified in such a way that these mice express only 50% of the NR1 subunit. The NR1 subunit is necessary for NMDA receptor channel function. We investigated the effects of reduced NMDA receptor function on cell proliferation in the hippocampus and the amygdala of the adult mouse brain. Transgenic (NR1+/-) and wild-type (NR1+/+) mice were injected with BrdU. We collected brain sections cutting through the rostro-caudal extension of the entire hippocampus of the NR1+/- and NR1+/+ (wild-type) mice. The phenotype of BrdU-positive cells was identified by double labeling with antibodies to neuronal or glial markers. Our results show that the NR1+/- mice, which express the NMDAR NR1 subunit at a low level, have a significant (p<0.01) increase in the number of BrdU-positive cells in the dentate gyrus and the amygdala compared to NR1+/+ mice. Some of these dividing cells express the neuronal marker NeuN. Our results indicate that low expression of the NR1 subunit significantly increases cell proliferation and neurogenesis, suggesting that low NMDARs activity contributes to the increase in cell proliferation in the adult brain.