Shuttle Computer Analysis System And Kaixinsan Improve Depression, Cognitive Dysfunction,

Depression is a serious and highly prevalent disorder characterized by long-termbad mood and anhedonia.Apart from mood disorder,cognitive dysfunction is a mostimportant feature in depressive patient.It is important to research the mechanism ofcognitive deficits accompanying depression and seek effective antidepressant agentswith the capability of enhancing cognitive function.Thus,this thesis includes two parts:1)establishment of a new computer-aided controlling and image analysis system forshuttle box(CISB);2)research of preventative action of Kai-Xin-San(KXS)waterextract on depressive-like symptoms and cognition deficit induced by chronic mildstress(CMS).Firstly,by combining the advantage of video tracking,image analysis,computerinformation processing and data mining,the CISB was developed with MicrosoftVisual C++6.0 computer language,which can collect and analyze the behavioral dataof rats in real-time.9 new parameters(DPM,DAM,SAA,SPE,SAT,EAT,LFC,ECRand TND)were established to evaluate cognitive function except for 6 presentindicators(AA,PE,RTAA,RTPE,EF and ITC).Simultaneously,the system wasvalidated with young rats,mid-aged rats and cerebral ischemia rats.The resultsdemonstrate that CISB is highly reliable and accurate,and can more systematically andsensitively evaluate the cognitive behavior from multiple aspects including theassociative learning and memory,understanding,processing speed and decisionmaking compared with present parameters.Animal behavior activities can beautomatically recognized,collected and analyzed,the animal video image and itsmoving track in shuttle box also can be played on the computer screen.Secondly,we explored the antidepressant-like and nootropic effects of a waterextract of KXS(at doses of 0.3,0.9,and 2.7g/kg/day)and ginsenoside Rgl(at doses of50,100mg/kg/day)(the effective ingredient of ginseng,which is the principal herb ofKXS)using chronic mild stress(CMS)as a well-validated model of depression.Theresults indicated that KXS and Rgl can significantly reversed the depressive symptomsin CMS model,such as decline in sucrose preference index and prolongation of latencyto feeding.Furthermore,KXS(0.9,2.7g/kg)and Rgl(50mg/kg)can also improve thecognitive impairment induced by CMS in the shuttle-box test such as increased numberof passive escapes and passive movement distance as well as decreased number of active avoidances,active movement distance and active response speed in CMS model.Biological investigation with HPLC-ECD,ELISA assay and immunohistochemicalmethods demonstrated that KXS and ginsenoside Rgl can inhibit increased AChEactivity of hippocampus;increase monoamine neurotransmitter concentration ofprefrontal cortex and hippocampus;upregulate the CREB and BDNF activities in thehippocampus and prefrontal cortex and reduce ACTH concentrations in the serum inCMS rats.Taken together,these results indicated that KXS and Rgl can exertantidepressant-like and nootropic effects in the CMS model by modulating multiplecentral nervous systems.Moreover,the effects of KXS were comparable to Rgl ondepression and cognitive dysfunction in CMS model.In conclusion,a highly automatic and intelligent CISB apparatus as well as a setof evaluation index were established,which can objectively,scientificly,systematically evaluate the behavior activities from multiple aspects in differentdementia animal models.Furthermore,antidepressive-like and nootropic effects ofKXS and Rgl were validated,and their mechanism were explored.It might be possibleto provide a potential drug for the treatment of depressive mood disorders andcognitive dysfunction induced by depression.