Involvement Of CRFR1 In Intermittent Hypoxia-exposed Neonatal Mice Spatial Learning And Memory

Hypoxia is one of the main stresses that creatures may encounter in their natural activities, the ability that creatures including human beings response to hypoxia are essential for postnatal development, behavior and health. Our previous study has indicated that neonatal mice exposure to three or four weeks moderate intermittent hypoxia (2000m,16.0%O2,4h/day) can promote spatial learning and memory, which is highly related to the level of CREB phosphorylation, enhancement of long-term potentiation (LTP) in hippocampal CA1 pyramidal neurons, and up-regulation of dendritic spines structural protein SPAR (a spine-associated RapGAP) and postsynaptic density protein PSD-95, etc.In this study we have used real-time quantitative PCR, Elisa, pharmacological and behavioral methods to investigate if and how CRF and its receptors are involved in the regulation of spatial learning in neonatal mice. Results showed that neonatal mice exposure to IH led to the up-regulation of hippocampal CRF protein, CRFR1 mRNA expression and IGFBP2 protein. We also found that intermittent hypoxia can promote the expression of IGFBP2 in hippocampus, and IGFBP2 and SPAR were positively correlated, whose effect could be blocked by IGFBP2 antibody. In addition,0.1nM CRF could induce IGFBP2 expression in primary culture hippocampus neurons. These findings suggest that neonatal intermittent hypoxia increases CRF expression in the hippocampus, which induces IGFBP2 through CRFR1 receptors, so as to promote dendritic spine structural protein SPAR and enhance neonatal spatial learning in mice.