| Objective:Stress is systemic and nonspecific reactions to social and psychological negative stimuli.Serious or long-term stress might cause great harm to health.The incidence of stress related disorders such as anxiety,depression and post-traumic stress disorder syndrome(PTSD)have been incresased in recent years.A rat model of chronic stress was established by using inescapable footshock method.The effects of chronic stress on hippocampus PKMζ expression and emotional behaviors were investigated by adopting the behavioral and molecular biology methods.The rssearch mighe provide new ideas for the treatment and prevention of chronic stress related diseases.Methods:1.A rat model of chronic stress :SD rats weighting 140g-150 g was used in the experiments.The current intensity of 0.8mA non-escaped foot shock was 40 min a day and continued for 5 days.2.Open field test : The behaviors of exploring and anxiety was examined by using open field test.The rats were placed in the center of open field and the activities of the rats were recorded and analyzed in 3 min.3.Water maze test: Which was used to study the special learning and memory abilityof rats.The nagiation task was tested for 5 days and the space exploration was examined in the sixth day.The escape latency and path was recorded and analyzed after the rats was placed into the pool from any point of the four quadrants facing the pool wall.In the space exploration experiment,the crossing times of the original platform and the time spent in the platform quadrant was recorded after the platform was removed.4.Molecular methods: The expression of PKMζ,p-PKMζ,I group of mGluR and PKC were examined and compared between the stress group and control group using Western blot method.Result:1.The stress rats decreased significantly in the total distance,central activity distance,time in the central area,average speed and frequency of rearing compared with the control group in the open field test(P<0.05),suggesting that the chronic stress rats reduced in self-exploratory behavior and increased significantly in anxiety level.2.The Morris water maze showed the escape latency of the stress group prolonged compared with the control group in the fourth and fifth day.However,the difference is no significant(P > 0.05).The total distance to find the platform increased increased significantly in the stress group in the fifth day.There is no significant difference in platform crossing and target platform time between the stress group and the control group in the sixth day.The results suggest that chronic stress decreased the spatial learning ability of rats,but did not affect the ability of memory.3.PKM is an atypical PKC family subgroup,containing PKCζ independent catalysis domain,without a regulatory domain.Western blot indicated that the expressions of PKMζ and P-PKMζ increased significantly in the hippocampus of stress group compared with the control group(P < 0.05).4.I group of mGluR has two subtypes of mGluR1 and mGluR5 with downstream PKC signaling pathway.Western blot results showed that the stress rats had higher expression of mGluR1,mGluR5 and PKC.The difference is significant(p < 0.05).Conclusion:Chronic stress up-regulated the expressions of PKMζand p-PKMζ while decreased the expressions of I group of mGluR and its downstream PKC in the hippocampus.PKMζand p-PKMζ up-regulation were possibly responsible for the nociceptive memory associated with chronic stress,which caused a decrease in self-exploratory behavior and higher levels of anxiety after chronic stress.The decreased expressions of I group of mGluR and its downstream PKC might injure the spacial learning ability of rats.This study may provide new ideas for the prevention and treatment of chronic stress related diseases. |
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