Intermittent hypoxic preconditioning relieves fear and anxiety behavior in post-traumatic stress model mice / 生理学报

Intermittent hypoxia (IH) has preventive and therapeutic effects on hypertension, myocardial infarction, cerebral ischemia and depression, but its effect on post-traumatic stress disorder (PTSD) has not been known. In this study, we used inescapable electric foot shock combined with context recapture to build PTSD mouse model. The levels of fear and anxiety were valued by the open field, the elevated plus maze (EPM) and the fear conditioning tests; the level of spatial memory was valued by Y maze test; the number of Fos positive neurons in hippocampus, amygdala and medial prefrontal cortex was valued by immunohistochemical staining; and the protein expressions of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and brain derived neurotrophic factor (BDNF) in these brain area were valued by Western blot. The results showed that IH and model (foot shock) had an interaction on percentage of entering open arms (OE%) in EPM and freezing time and the number of fecal pellets in fear conditioning test. IH increased OE% in EPM and reduced the freezing time and the number of fecal pellets in fear conditioning test in PTSD model mice. At the same time, IH reduced the number of Fos positive neurons in the hippocampus, amygdala and medial prefrontal cortex of PTSD model mice, and increased the protein expression levels of HIF-1α, VEGF and BDNF in these brain tissues. In conclusion, IH pretreatment can relieve fear and anxiety behavior in post-traumatic stress model mice, suggesting that IH may be an effective means of preventing PTSD.

Effects of CHL1 deficiency,a cell adhesion molecule,on the inflammatory bowel disease / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of deficiency of CHL1 in inflammatory bowel disease (IBD).@*METHODS@#Dextran Sulfate Sodium (DSS)-induced colitis model was used to study the effects of deficiency of CHL1 on the development of IBD. Ten CHL1(+/+) mice in C57/BL6 background were randomly divided into CHL1(+/+) group and DSS-induced CHL1(+/+) group. Ten CHL1(-/-) mice in C57/BL6 background were randomly divided into CHL1(-/-) group and DSS-induced CHL1(-/-) group. DSS-induced CHL1(+/+) group and DSS-induced CHL1(-/-)group were fed with 1.5% DSS for 7 days, and then drinking distilled water for 2 days. CHL1(+/+) group and CHL1(-/-) group as control group were fed with distilled water for 9 days. The changes of weight, survival, fecal blood and the change of colon length in this study were observed.@*RESULTS@#On the 7 day, the weight of DSS-induced CHL1(-/-) group were reduced significantly, and DSS-induced CHL1(-/-) group had extreme mortality on the 9th day. The fecal blood of DSS-induced CHL1(-/-) group also had higher score than that of DSS-induced CHL1(+/+) group. In the DSS-induced CHL1(-/-) group,the length of colon was shortened obviously.@*CONCLUSIONS@#The loss of CHL1 aggravates the development of IBD.

Effect of high altitude hypoxia on cognitive flexibility / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To explore the effects of high altitude on cognitive flexibility.</p><p><b>METHODS</b>Simulated hypoxia at an altitude of 3 600 m was performed in a hypobaric chamber. Twenty-three volunteers without hypoxic experience were selected and the mean age was about 25.1 years. The physiological parameters (heart rate, blood pressure and oxygen saturation) were measured. Task switch paradigm was used to explore the cognitive flexibility in each phase, and the changing anxiety state was evaluated simultaneously.</p><p><b>RESULTS</b>Reaction time (RT) switch cost in hypoxia phase showed a significant increase compared with the baseline; anxiety level in hypoxia phase was higher than the adaptation phase; a remarkable negative correlation between anxiety level and RT switch cost was found in adaptation phase, whereas a positive correlation was found in landing phase.</p><p><b>CONCLUSION</b>High altitude (3 600 m) affects cognitive flexibility and anxiety state. Anxiety before the hypoxia exposure improves the cognitive flexibility performance, while anxiety after the hypoxia exposure hampers the performance because of the post-hypoxia effect.</p>

The effects of autophagy on cell survival under different hypoxia / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the regulation of different hypoxia on cell survival and autophagy.</p><p><b>METHODS</b>PC12 cells were treated with different hypoxia. The cell survival was measured by MTT assay, expressions of LC3 and p62 were marked for autophagy detected by Western Blot, and the level of reactive oxygen species (ROS) was analyzed by flow cytometry.</p><p><b>RESULTS</b>The cell viability was different under different hypoxia: moderate hypoxia promoted cell viability, and severe hypoxia caused a decrease in cell viability; autophagy marker molecules, p62 and LC3-II expressions were different: moderate hypoxia increased p62 and LC3-II expressions, in contrast, severe hypoxia led to the decrease of p62 and LC3-II expressions; compared to normoxia, moderate hypoxia did not change the levels of ROS, while severe hypoxia increased the levels; 3-MA, the inhibitor of autophagy, elevated the levels of ROS in the three oxygen concentrations, additionally, the increased amplitudes in the moderate and severe hypoxia groups were higher than that in the normoxia group.</p><p><b>CONCLUSION</b>Moderate hypoxia promotes cell survival, severe hypoxia causes the cell death, and the autophagy activity may mediate the effects of different hypoxia.</p>

Influence of acute hypoxia on CHL1 expression in different tissues of mice / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the effects of acute hypoxia on the cell adhesion molecule close homologue of L1 (CHL1) expression in different brain areas and main organs (heart, lung, kidney) of mice, and provide a basis for the role of CHL1 in hypoxia injury.</p><p><b>METHODS</b>Mice were randomly divided into two groups (n=10): normoxia group and hypoxia group. Hypoxia group were treated by acute hypoxia (8% O2, 8 h). Protein expression changes in different tissues were evaluated by Western blot.</p><p><b>RESULTS</b>In central nervous system, CHL1 protein expressions were down-regulated in cerebral cortex, hypothalamus and brain stem by acute hypoxia and up-regulated in cerebellum. In heart and lung, CHL1 protein expression were down-regulated by acute hypoxia.</p><p><b>CONCLUSION</b>CHL1 protein expressions were changed in different tissues after acute hypoxia, which suggested CHL1 might play an important role in hypoxia damage regulation.</p>

Effect of low glucose and/or hypoxia on the proliferation and metabolism of neural stem cells / 中国应用生理学杂志

<p><b>OBJECTIVE</b>Recent study demonstrated that hypoxia could regulate the proliferation and differentiation of neural stem cells in vitro. In the present study, effects of low glucose and/or hypoxia on the proliferation and metabolism of neural stem cells were investigated in vitro.</p><p><b>METHODS</b>The neural stem cells were isolated from the rat embryonic mesencephalon (E13.5), and exposed to different oxygen concentrations (low oxygen: 3% O2 or normoxia: 20% O2) and different glucose concentrations (high glucose concentration: 4.5 g/L and low glucose concentration: 1.4 g/L) for 3 days. The proliferation of neural stem cells were examined by CCK-8 assay. Furthermore, the content of glucose, lactate, and pyruvic acid in the medium were measured after cultured in different condition for 1, 3, 5 days.</p><p><b>RESULTS</b>Low oxygen and low glucose could increase the proliferation of neural stem cells respectively; in addition, the number of neurospheres under both low oxygen and glucose was the most among the four groups. The content of glucose and pyruvic acid in the medium from low oxygen or low glucose condition decreased, while the lactate concentration increased compared with the control group.</p><p><b>CONCLUSION</b>The results indicate the neural stem cells prefer grow under the low glucose and low oxygen condition, and that is mainly under going glycolysis to maintain its self-renew ability. This study may provide us a useful clue for application of neural stem cells transplantation.</p>