The effect of hypoxia on the functional and structural development of the chick brain.

Decreased oxygen availability during gestation is linked with altered structural development of the brain and cognitive deficits after birth. Prehatch hypoxia can induce gross neuropathology such as brain lesions or more subtle injury including selective neuronal cell loss, white matter injury and gliosis. In the current study we used the developing chick embryo to determine whether 24h of hypoxia at different prehatch ages, embryonic day 10, 12 or 14 (E10, E12 or E14), resulted in an alteration in neuronal cell number or astrocyte density in brain areas associated with learning and memory. Twenty-four hours of hypoxia (14% oxygen) commencing at E10 resulted in an increase in the density of GFAP-positive astrocytes in the medial striatum (MSt) (P<0.05) and a significant reduction in the number of NeuN-positive neuronal nuclei in the intermediate medial mesopallium (IMM) (P<0.02). Hypoxia at E14 resulted in an increase in GFAP immunoreactivity in the hippocampus (P < or = 0.02) and a significant decrease in the number of NeuN-positive cells in the IMM (P<0.04). Memory was tested soon after hatch using a bead discrimination learning task and results showed that E10 hypoxia significantly reduced short-term memory, which subsequently affected all stages of memory formation (P<0.001), whereas 24h of hypoxia at E14 did not alter short-term memory, but impaired consolidation into long-term memory (P<0.02). Interestingly, 24h of hypoxia at E12 did not alter GFAP immunoreactivity or NeuN-positive cells, nor did it result in memory deficits. We find that an alteration in the number or a disruption in the normal development of astrocytes and neurons significantly affects memory formation and consolidation in the young chick.