Study For Neurobiology Mechanism Of "Kidney Storing Will And Responding To Fear" And Tonifying Kidney Prescription And Herb's Mechanism

ObjectiveAccording to the emotion theory of traditional Chinese medicine (TCM) deems that kidney stores will and response to fear, and this theory is the guide line of this research. The cut into point of this research is the fear response and memory. And the research though of this study is based on according pathology and efficacy deduce to physiology. The study including the formation, consolidation, extraction and extinction of fear memory, and the plasticity of amygdala-hippocampus-prefrontal cortex nervous pathway, as well as the results of pharmacological studies of prescriptions and herbs for invigorating the kidney. After this study, we aim to reveal the material basis, the action modes, and the neurobiological mechanisms of the kidney in controlling and regulating emotional activity. Moreover, there will be a supplement and innovation for the scientific content kidney store will and response to fear after this study. And show this scientific content's own value in the modern mental psychology. Methods1 To construct two kinds of kidney deficiency animal model.2 The formation and extraction of fear memory experiment.This experiment was trained the rats with conditioned stimulus (CS) and unconditioned stimulus(US) to form conditioning fear, and freezing time was used as index. The experiment was study the affection of kidney deficiency and tonifying kidney prescription and herb's on the formation, consolidation and extraction of fear memory.3 Fear memory extinction training experiment.Trained rats with fear extinction training after their fear conditioning was constructed, and freezing time was used as index. This experiment was studied the affection of kidney deficiency and tonifying kidney prescription and herb's on the fear memory extinction.4 The study of the conditioning fear response plasticity of amygdala-hippocampus- prefrontal cortex nervous pathway.This experiment was divided into two stages to study the plasticity of amygdala-hippocampus-prefrontal cortex nervous pathway both on fear memory formation and extraction and fear memory extinction. To explore the pathology mechanism of kidney deficiency affect by fear and the effective of tonifying kidney proscription and herbs. In order to reveal the material basis, the action modes, and the neurobiological mechanisms of the kidney in controlling and regulating emotional activity. The detect indexes of this study were as below. Immunohistochemistry and in situ hybridization were used to detect CREB, MAPK, GABAα1R and NR2B in the amygdale, hippocampus and prefrontal areas. In situ hybridization was used to detect CREB and MAPK in the same brain areas.Results1 Repeatedly afforded CS and US associated stimulus were increasing the laboratory rats' freezing time significantly, but the CS and US unassociated stimulus didn't work.2 Kidney deficiency rats' MAPK, GABAα1,R, NR2B in hippocampus area and CREB,NR2B in amygdala area and NR2B in prefrontal cortex area's expression were up regulated. And conditioning fear stimulus further active the expression of NR2B in these brain areas. Moreover, the expression of CREB in amygdala area and GABAα1R in hippocampus area were also up regulated.3 The tonifying kidney prescription Guiluerxiangao were up regulated the GABAα1R expression in hippocampus area and downregulated the GABAα1R in amygdala area in the aged rats. Meanwhile, Guiluerxiangao were down regulated the expression of CREB, GABAα1R, NR2B in the hippocampus area and CREB, MAPK in amygdala area in the over sex rats. Moreover, Guiluerxiangao down regulated the over sex rats'expression of CREB both in hippocampus and amygdala area, and down regulated the expression of NR2B in hippocampus area. Tonifying kidney proscription were down regulated GABAα1R expression in hippocampus area of over sex rat; but up regulated aged rats'GABAα1R expression in hippocampus area and down regulated GABAα1R expression in amygdala area.4 All rats'freezing time were significantly shorter compare to their control group after fear memory extinction training, but the tonifying kidney proscription and herbs didn't promote the fear extinction.5 Over sex rats'expression of CREB, MAPK, GABAα1R, NR2B in hippocampus area and MAPK in amygdala area were down regulated.6 The tonifying kidney proscription Guiluerxiangao up regulated the expression of CREB, NR2B in hippocampus area and GABAα1R in amygdala area. But, inhibit the expression of MAPK in amygdala area. All these regulations were in over sex rats that after fear extinction training.Conclusion1 Repeatedly afforded CS and US associated stimulus to the laboratory rats could form conditioning fear memory, but the CS and US unassociated stimulus didn't work.2 Kidney deficiency rats acted the expression of NR2B in hippocampus area, amygdala area and prefrontal cortex area to deduce Long-term potentiation (LTP) in these areas, which in order to form conditioning fear memory. Meanwhile, the expression of MAPK in hippocampus area was acted and LTP in this area was formed. Moreover, conditioning fear stimulus further acted NR2B in all three areas, in order to form fear memory by the formation of LTP. In addition, the change of GABAα1R express in the hippocampus area also one of the role that conditioning fear memory is form.3 The tonifying kidney proscription Guiluerxiangao inhibit the long term memory through down regulated the expression of CREB in all three brain areas. Meanwhile, down regulated the NR2B in hippocampus area to inhibit the synaptic plasticity and memory in this area. The expression change of GABAα1R in hippocampus area and amygdala area also one of the role that conditioning fear memory form.4 The tonifying kidney proscription Guiluerxiangao inhibit the long term memory through down regulated the expression of CREB in all three brain areas, and inhibit long term memory, in order to extinction fear memory. Meanwhile, fear extinction training down regulated the expression of NR2B in hippocampus area to inhibit the synaptic plasticity and memory in this area. Moreover, the expression of MAPK in hippocampus area and amygdala area were down regulated, and these inhibit the action of CREB were in order to inhibit the formation of long term memory. In addition, down regulated the expression of GABAα1R in hippocampus area to reduce its negative action to the new learning is one of the mechanism of fear extinction.5 The tonifying kidney proscription Guiluerxiangao down regulated the expression of NR2B in hippocampus area in the over sex rat after fear extinction to inhibit and end the fear extinction. Meanwhile, up regulated the expression of CREB in hippocampus area could enhance the formation of long term memory. Moreover, inhibit the expression of MAPK in amygdala area is one of the mechanism of this medicine inhibit the fear extinction. In addition, up regulated the expression of GABAα1R in amygdala area to enhance its postive action to the new learning is one of the mechanism of fear extinction.