Rodricks Candice L, Gibbs Marie E, Castillo-Melendez Margie, Miller Suzanne L
Department of Physiology, Monash University, Victoria 3800, Australia.
Int J Dev Neurosci. 2010 Jun;28(4):343-50. doi: 10.1016/j.ijdevneu.2010.02.004. Epub 2010 Feb 18.
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.
妊娠期氧供应减少与大脑结构发育改变及出生后认知缺陷有关。孵化前缺氧可诱发严重的神经病理学变化，如脑损伤，或更细微的损伤，包括选择性神经元细胞丢失、白质损伤和胶质增生。在本研究中，我们利用发育中的鸡胚来确定在不同的孵化前年龄，即胚胎第10天、12天或14天（E10、E12或E14）进行24小时缺氧，是否会导致与学习和记忆相关脑区的神经元细胞数量或星形胶质细胞密度发生改变。从E10开始的24小时缺氧（14%氧气）导致内侧纹状体（MSt）中GFAP阳性星形胶质细胞密度增加（P<0.05），中间内侧中脑皮质（IMM）中NeuN阳性神经元细胞核数量显著减少（P<0.02）。E14缺氧导致海马中GFAP免疫反应性增加（P≤0.02），IMM中NeuN阳性细胞数量显著减少（P<0.04）。孵化后不久，使用珠子辨别学习任务对记忆进行测试，结果表明，E10缺氧显著降低了短期记忆，随后影响了记忆形成的所有阶段（P<0.001），而E14的24小时缺氧并未改变短期记忆，但损害了向长期记忆的巩固（P<0.02）。有趣的是，E12的24小时缺氧并未改变GFAP免疫反应性或NeuN阳性细胞，也未导致记忆缺陷。我们发现，星形胶质细胞和神经元数量的改变或正常发育的破坏会显著影响幼雏的记忆形成和巩固。
