Study On The Learning And Memory And Hippocampus Molecular Mechanism Of Depressed Rats Based On Clinical Method Of Waking Up The Spleen And Relieving Depression

Depression is a kind of psychosomatic disease which seriously damages body and mind of patients,it not only results in depression and a variety of physical symptoms of patients,also to cause a decline in cognitive function of patients comprehensively,the patients cannot adapt to the normal social and daily life activities.Patients with severe depression also can appear suicidal thoughts and behavior.According to statistics,about 15%of the patients with depression death caused by suicide.Depression not only severely affects the patient’s life and work,also brings heavy mental and economic burden for their families and society.Depression has a high incidence,high recurrence rate,and the characteristics of the delayed course.According to the relevant research,it shows that depression has affected 20%of the world’s population[1].According to the world health organization(WHO)predicts that by 2020 depression will gradually develop into the second disease burden serious illness,which becomes a major public health problem that cause serious damage to public health[2].It’s reported that for depression patients,impairment in cognitive function and memorizing is another more important reason for negative self evaluation,besides the depressed emotion and physical discomfort.Researches also show that dysmnesia and learning disorder may last even after the physical discomfort and depressed cured,which are also considered be highly responsible for the recurrence of depression and become to draw increasing attention experts national and abroad in recent years.However,the mechanism of its development is still not clear.Dysmnesia and learning disorder along with the depression may be influented by many factors,such as type of depression,course,situation,frequency of onset,age,i.e.Studies have shown that the complicated bio-mechanism is involved with HAP-axis-related hormones,glutamate,5-HT,and cAMP-PKA-CREB,ERK signaling as well as neurotrophic factors.Emotion reacting and learning and memorizing are in different reflecting regions of brain,but there is overlapping region and interaction in brain loop.Dysmnesia and learning disorder due to depression is mainly related to Medial temporal lobe system including hippocampus and amygdale prefrontal cortex and diencephalons.Besides,abnormal brain potentials on P300 and N400 can be detected in depression patients with dysmnesia and learning disorder.In traditional Chinese medicine,depression pertains to ’depression syndrome’.Liver depression and qi stagnation syndrome,liver depression and spleen deficiency syndrome,liver depression and kidney deficiency syndrome are the most common syndromes in clinic,and there is interrelation between them in pathogenesis.In early stage of depression,main pathogenesis is liver depression and qi stagnation,and later wood will subjugate earth,which leads to spleen deficiency,or liver depression and kidney deficiency due to spleen deficiency involving kidney or aging.Liver depression and spleen deficiency is the core pathological changes of dysmnesia and learning disorder,with the clinical manifestation of depressed emotion,anxiousness,poor appetite,lassitude and weakness lassitude and weaknesslassitude,poor memory,decreased concentration,pink or pale tongue,and thin or wiry pulse.Spleen is regarded to be responsible for the function of learning and memorizing in TCM.Because spleen deficiency would lead to lack of qi and blood,and consequently causes insufficiency of brain,or it leads to disorder of fluid metabolism,further induces phlegm formation that disturbs or block the orifice in brain,and either will eventually results to impairment of learning and memorizing.Apparently,irregularity of NEI net work,brain electrical physiological dysfunction,and disorder brain gut axis may be involved in depression of liver depressed and spleen deficiency syndrome.The animal model of that syndrome is mainly established by means of chronic restraint stress.At present,the antidepressant drugs are widely used in clinical,some studies suggest it has certain improve the ability of learning and memory,executive function,such as cognitive impairment,but it is disappointing in clinical application.For the treatment of patients with depression,gradually from the traditional simply antidepressant treatment,developing to cure depressed mood,somatic symptoms,comprehensive rehabilitation of cognitive dysfunction,to better control the depression,prevent of recurrence,and improve their adaptability to society and life.TCM clinical treatment or animal experimental intervention used more in classical prescriptions of Traditional Chinese Medicine of Xiaoyao powder as a representative,the formulas have the role of relieving Liver stagnation Spleen deficient,which obtains the good curative effect[3].Clinical research:Objective:to study the TCM pathogenesis about the depression associated with cognitive impairment in patients.Methods:screening 180 cases of patients with depression conforming to the standard,then according to the MoCA scores,grouping the patients,respectively compared with MCI depression group and not MCI depression group,for the facors of TCM syndrome characteristics of depression patients.Results:depressed patients with MCI depression,compared to depressed patients without MCI,the phlegm damp syndrome elements more prominent,statistically significant(P<0.05),the hot pathogenesis less,statistically significantly(P<0.05).Conclusion:cognitive dysfunction of depression is proportional to the degree of phlegm dampness,it is closely related to the physiological function of spleen,pathological evolution of spleen.Presumably,phlegm dampness may be the core of TCM pathogenesis of cognitive impairment of the depression,Liver stagnation Spleen dampness may be the basic pathogenesis of cognitive dysfunction of depression.Basic Research:Objective:Preliminary discussion the effects of XingPiJieYu method to depression,learning and memory,the influence of hippocampal structure and its molecular mechanism form the rats.Methods:The present study was randomly divided into six groups:the normal control group;the model control group;the high,middle and low dosage groups of Xingpijieyu Decoction(XPJY);the sertraline group.Chronic unpredictable mild stress for 21 days and the social isolation method were used to establish depression models in rats.The sugar water preference test and open-field test are used to evaluate depressive behavior in rats.The Morris water maze was used to evaluate the learning memory capability.The radioimmunoassay,Western Blot and RT-PCR Method were carried out to determine the expression levels of the cAMP-PKA-CREB-BDNF signaling pathway.Results:After 21 days,the preference for sugar solution in the model control group significantly decreased,while the open field test in the model control group significantly increased compared to the normal group.These results indicate that the depression models were successfully established.In contrast,the period for the water maze significantly increased,indicating that the learning memory capability in the model control group significantly decreased in comparison to that in the normal group.Meanwhile,the expression levels of the protein in the cAMP-PKA-CREB-BDNF signaling pathway in hippocampus in the rats from the model control group significantly decreased.In comparison to the model control group,the XPJY high dosage group showed significantly improved depression,learning memory capability and expression levels of the cAMP-PKA-CREB-BDNF signaling pathway in the model rats.In terms of improving learning and memory behavior in rats,Chinese traditional medicine shows the even stronger trend than sertraline.