Abstract
PURPOSE: Intermittent hypoxia (IH) is associated with learning/memory dysfunction during the early growth period. However, the sex- and subregion-specific brain vulnerability to IH and its effects on learning, memory, and emotional stability in infants remain unclear. This study investigated sex- and subregion-specific vulnerability to IH in the hippocampus, relating to memory and learning, and in the amygdala, relating to early emotional development in infant rats. METHODS: Thirty-six 1-week-old Sprague-Dawley rats were exposed to IH (IH group) or normoxic air (N group). Learning/memory functions, emotional behavior, and locomotor activity were examined using the Y-maze apparatus, passive avoidance, and open field tests. The hippocampal cornu ammonis (CA) 1 and CA3 regions, dentate gyrus (DG), and amygdala were examined to measure Ntrk2, Hif1a, and Epas1 expressions. A two-way analysis of variance followed by Tukey-Kramer's honestly significant difference post-hoc analysis, or non-parametric equivalents and independent t-test were used to assess the data. RESULTS: IH exposure negatively regulated long-term spatial memory and anxiety in male and female rats and short-term spatial memory in male rats. IH effects on brain development were validated by the increased expression of Ntrk2 and Epas1 mRNA in the DG, Ntrk2 and Hif1a mRNA in the amygdala, and an increase in the immunohistochemically stained areas in the DG and amygdala of only male rats. CONCLUSION: These findings provide in vivo evidence for sex- and subregion-specific functional linkages between cognitive function and IH, and between anxiety tendency and IH during the early growth period.