Effects And Mechanisms Of Hypoxic Training On The Neurons In Rat Hippocampus

The effects and mechanisms of hypoxic training on the neurons in rat hippocampus were studied at whole body, cell and molecular levels. 90 rats were selected from 120 male SD rats (6 week old) by exhaustive test and randomly divided into 9 groups: living-low control group (Li: live in normoxia), living-high control group (Hi: live in hypoxia), intermittent living-high control group (LH: live in hypoxia 12hr/d, live in normoxia 12hr/d), living-low training-low group (LoLo: live in normoxia, train 1hr/d), living-high training-high group (HiHi: live in hypoxia 11hr/d, train 1hr/d), living-high training-high and recovery 1 week group (HiHi-Lo: live in hypoxia 11hr/d, train 1hr/d, 6 weeks; live in normoxia, train 1hr/d, 1week), living-high training-low group (HiLo: live in hypoxia 12hr/d, live in normoxia 11hr/d, train in normoxia, 1hr/d ), living-high training-low and recovery 1 week group (HiLo-Lo: live in hypoxia 12hr/d, live in normoxia 11hr/d, train in normoxia, 1hr/d 6 weeks; live in normoxia, train 1hr/d, 1week), living-low training-high group (LoHi: live in normoxia 23hr/d, train in hypoxia, 1hr/d ), each group with 10 rats. During the 6 weeks experimental period, we employed the 13.6% concentration of oxygen (equal to altitude 3500m) in the hypoxic chamber. The rats of hypoxic training were introduced to treadmill. The speed of running was set by blood lactate-speed curve. The speed of training was 30m/min in hypoxia, 35m/min in normoxia. The rats were trained 6d/week and were sacrificed after 6 weeks.The exercise ability of rats in training group was tested after 4 weeks training. The result was that the exercise ability of rats in HiLo and LoHi group was higher significantly than LoLo and HiHi groups after 4weeks training.Using HE staining, we observed the morphological changes in rat hippocampus neurons. It was showed that the neurons of HiHi were degenerated slightly, and the neurons of HiLo and LoHi groups were natural. There were no apoptotic cells in any groups testing by terminal deoxynuleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique.The mRNA level of HIF-1α, EPO, GLUT1, VEGF in rat hippocampus tissue were investigated by Real Time fluorescence Quantitative PCR to study the mechanism relevant to the effects of hypoxic training on neurons in rat hippocampus. The results showed that the mRNA level of HIF-1αwas increased significantly in HiHi and HiLo groups. The mRNA level of EPO was increased very significantly in HiHi and HiLo groups, and increased significantly in LoHi group. The mRNA level of VEGF was increased very significantly in HiHi and HiLo groups, and increased significantly in LoHi group. The mRNA level of GLUT1 was increased very significantly in HiHi group, and increased significantly in HiLo group. It was very similar between the increasing mRNA level of HIF-1αand he increasing mRNA level of EPO, GLUT1, VEGF after 6 weeks hypoxic training.Through the above research, logical induction led to the following: Of all the chemical elements, oxygen is the most vital to the human body. The brain is the most sensitive organ to oxygen deprivation (hypoxia). Hypoxia and/or training induced hypoxia to brain activate hypoxia-inducible factor-1 (HIF-1), which in turn activates gene transcription of HIF-1 target genes, such as EPO, VEGF, and GLUT1. EPO and VEGF then confer cellular protection. VEGF mainly prevents apoptosis and stimulates proliferation of endothelial cell, resulting in new vessel growth (angiogenesis) and ultimately better oxygenation of hypoxic tissues. The increase in GLUT1, and the increase in capillary density, results in an increase in the transport capacity for glucose transport across the blood-brain barrier. The effects of these on brain are contribution to neuronal survival. It can enhance the ability of brain to resist the hypoxia. The brain may adapt to the hypoxic training and can tolerate low oxygen environment induced by training. Thus the ability of exercise is been accelerated.