Altitude Hypoxia On Hippocampal Neurons Nmda Receptor In Developing Rats

A Study on the effect of hypobaric hypoxia on theNMDA receptor of the developing hippocampus neuronsABSTRACTThe present study was undertaken to observe the effect of hypobaric hypoxia on the expression of NMDAR1 mRNA and somatostatin mRNA, the kinetic properties of NMDA receptor channel, the ultrastructure of hippocampus neurons synapse, leanrning and memory in the model of developing rats with hypobaric hypoxia by using in situ hybridization, transmission electron microscopy, patch-lamp and active avoidance reaction training and Morris water maze training techniques. The objective is to explore the effects of hypobaric hypoxia on the neuron development. The results were as follows:1.At the early period of newborn rats following hypobaric hypoxia, the expression of NMDAR1 mRNA and somatostatin mRNA in hippocampus was markedly increased, and maintained at high level for certain period. After long-term hypobaric hypoxia, the expression of the two mRINA was decreased. If rats pretreated with ketamine (ip, 40mg/Kg), a competitive antagonist of NMDA receptor, the expression of the somatostatin mRNA was inhibited.2.The expression of NMDARI mRNA and somatostatin mRNA in rats treated with fetus hypoxia was in a lower level than the control.3.Rats treated with newborn hypoxia or fetus hypoxia, the open probability of NMDA receptors channel in hippocampus neurons was reduced. Analyzed by Marquardt-LSQ fit, the open time constants was decreased, the close time constants is increased.4.Some of mitochondrion in hippocampus neurons swelled after longterm hypoxia, the number of negative curvature type synapses was decreased.5.During the active avoidance reaction, the speed of acquisition slowed in the newborn hypoxia or fetus hypoxia rats, while the speed of extinction is fasted. In the Morris water maze task, latency to find a hidden platform was longer and the frequency of pass through the platform was decreased in newborn hypoxia or fetus hypoxia rats than in control rats.The results suggest that the expression of NMDA receptor mRNA and the kinetic properties of NMDA receptor channel of hippocampus neurons is changed under the hypobaric hypoxia environment. These changes may affect the synapse plastic and the secretion of the somatostatin, and even the learning and memory at last.