Impaired adult neurogenesis associated with short-term memory defects in NF-kappaB p50-deficient mice.

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.

Members of the NF-kappaB family expressed in zones of active neurogenesis in the postnatal and adult mouse brain.

The Rel/NF-kappaB family of transcription factors is implicated in cell proliferation, cell death, cell migration and cell interactions. Here, we examined by immunohistochemistry the expression pattern of various members of this family during postnatal telencephalon development and during adulthood, and we used neuronal and glial markers to identify the cells types where they are expressed. Distinct Rel/NF-kappaB proteins are highly expressed postnatally in the subventricular zone and in the rostral migratory stream. In particular, Rel A and p50 are expressed in radial glial cells, in migrating neuron precursors and in a population belonging to the astrocytic lineage. Rel B, on the other hand, is only expressed in migrating neuron precursors, whereas c-Rel is present in a few cells located at the edges of the rostral migratory stream. The expression of Rel A and p50 persists into adulthood, particularly in subventricular zone astrocyte-like cells and in migrating neuron precursors, respectively. The selective expression of NF-kappaB members in the postnatal subventricular zone and rostral migratory stream and their persistence into adulthood in regions of ongoing neurogenesis suggests possible mechanisms linking NF-kappaB expression with cell proliferation and migration. Their presence in actively proliferating progenitor cells, detected by BrdU staining, further suggests that NF-kappaB may be part of a signaling pathway that is important for neurogenesis.