Impaired Adult Neurogenesis Associated with Short-Term Memory Defects in NF-κB p50-Deficient Mice

Abstract

Neurogenesis proceeds throughout adulthood in the brain of most mammalian species, but the molecular mechanisms underlying the regulation of stem/progenitor cell proliferation, survival, maturation, and differentiation have not been completely unraveled. We have studied hippocampal neurogenesis in NF-kappaB p50-deficient mice. Here we demonstrate that in absence of p50, the net rate of neural precursor proliferation does not change, but some of the steps leading to the final neuron differentiation status are hampered, resulting in approximately 50% reduction in the number of newly born neurons in the adult mutant hippocampus. Additionally, in p50(-/-) mice, we observed a selective defect in short-term spatial memory performance without impairment of hippocampal-dependent spatial long-term memory and learning. Our results highlight the role of NF-kappaB p50 in hippocampal neurogenesis and in short-term spatial memory.