| Chronic stresses in modern fast-paced way of life,high-intensity working and kinds of special environments induce serious physical and psychological changes,especially the changes of cognitive function,which has been one of the hot topics in neuroscience research.Restraint is one of the most widely modelling methods used to establish animal memory impairment model,which cause simple psychological stress through restricting animal movements.Therefore,to study the cognitive change rule and mechanism caused by chronic stress,and seek effective protective drugs are the current focus of the medical field.Animal behavior assessment is one of major means of evaluation of cognitive function,for example,shuttle-box,step-down,Morris water maze,step-through,etc.These traditional evaluating methods of cognitive behavior are established under the principle of avoiding punitive damages(electric shock,cold water).For during the testing animal respond to conditional stimulus passively,the animal abilities of interest,motivation,reactivity,judgement,decision making and learning&memory in a complex operation task could not be measured.Additional,those punitive stimulus influence the physiological and psychological health of animals.Therefore,we modified the reward directed instrumental conditioning test system based on the previous works,and established the cognitive evaluation technology and methods to assess the subtle cognitive behaviors including interest,motivation,response,discrimination,learning and memory,explore the characteristics of cognitive impairment induced by chronic stress.The main research content is as follows.1.We modified the reward directed instrumental conditioning and comprehensively evaluated the interest,response,motor function,discrimination,judgement,decision making,learning and memory ability when animal performed a complex workingWe have mastered the key technology to evaluate the subtle cognitive behaviors of animal under different combination of multi-stimulus including double levers,double rewards,and multicolor signal sequences.Based on the theory of animal psychology,experimental modes contains habituation training,reward conditioning,Instrumental learning,conditional reward devaluation,position signal discrimination,two-color visual signal discrimination procedure were established.Animal interest,response,motor function,discrimination,judgement,decision making and learning memory ability during performing the complex working could be comprehensively evaluate.Therefore,the new method established promoted the cross from simple task to complex task,from passive avoidance to active operation.2.The effects of chronic restraint stress on the cognitiove function was researched systemicallyResults showed that chronic restraint stress did not influence the rats' motor function and interest in reward.The data from instrumental conditioning showed that the pre-training chronic stress seriously damaged the acquisition of instrumental learning,which was reversed partially by increasing the intensity of training.And post-training chronic stress did not cause any damage to operant capacity,but induce the decline of operational efficiency.In the positon signal discrimination and two-color visual signal discrimination tasks,the chronic restraint stress significantly damaged the performance of animal,indicating a significant deficit in visual discrimination ability.3.Western blot were applied in this study,and preliminary illuminated that the BDNF-TrkB signal transduction pathway in prefrontal cortex are closely related to the damage of visual discrimination ability caused by chronic stressSignificantly increased MDA levels and decreased antioxidant enzyme activity(SOD,T-AOC?GSH)in prefrontal cortex compared to Con group were founded,indicating that oxidative stress is involved in impaired memory,and SOD,T-AOC?GSH and MDA may be responsible for impaired memory induced by chronic stress.Data from Western blot showed that the expression of BDNF,TrkB,Erkl/2?Egr-land Synapsin-1 in prefrontal cortex were significantly decreased in rats exposed to restraint stress over 28 days.The decreased expression of GR was also founded.In addition,the behavioral training in conditional visual discrimination task significantly increased the expression of these proteins in prefrontal cortex.Therefore,these results demonstrated that chronic restraint stress enhanced the corticosterone release,which bind to GR to down-regulate the BDNF/TrkB/Erkl/2 pathway and Egr-1,Synapsin-1 expression,inducing the cognitive deficits.4.Comparison of Rgl,Rbl for their effects on improving cognitive disorders induced by chronic restraint stress using the behavioral indicators of multi-level and multi-angle,providing potential candidates for protection of cognitive impairmentIn our study,we firstly evaluated the effects of Rgl and Rbl on cognitive function in reward instrumental learning.Our results showed that Rgl,Rb1 could obviously enhanced the performance in reward directed instrumental conditioning and the conditional visual discrimination tasks,demonstrating a good effect of improving cognitive function.Besides,Rgl appeared superior Rbl in reversing chronic stress-induced memory deficiency.In conclusion,we modified the reward instrumental conditioning,and established the detection and analysis technique for multiple aspects of cognitive ability,such as interest,response,motor function,discrimination,judgement,decision making and learning memory ability during performing the complex working firstly.Our new established reward instrumental conditioning was used in this study to evaluate the effect of chronic restraint stress on cognitive function and its mechanism,the results showed that chronic restraint stress not only damaged the rats' learning and memory,but also higher cognitive ability,such as reaction capacity,recognizing ability,judgment and decision making and so on.We also found that these affects were closely linked with the oxidative stress and BDNF signal transduction pathway in prefrontal cortex.On this basis,we proved the cognitive improvement effects of Rgl and Rbl,and providing two candidates for protection of cognition deficits.In aerospace medicine,chronic restraint stress was used to simulate the narrow and claustrophobic space environments in space flight in a certain extent.Therefore,the experimental results in this paper also indicated that the long narrow and claustrophobic space environment stress has little effects on physical fitness of the astronauts,but decreases the discrimination ability and the accuracy of the operation for the sophisticated tasks.Moreover,the serial of reward instrumental tasks established could simulate the astronaut operation.This is a feasible methods for the cognitive assessment underperforming the complex working in the conditioning of stress. |
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