Effects Of Fraction Of Cynomorim Songaricum Rupr EtOAc On Learning And Memory Fuction And Mechanism In Ovariectomized Rat Model

Estrogen is the necessary endogenous active compound to maintain the normal the physiological functions of women.In central nervous system,estrogen not only acts on genital related with hippocampal circuit to affect learning and memory.Many animal experiment studies demonstrated that estrogen had neuroprotective effect and could promote learning and memory,but the mechanisms of these actions are very complicated.Cynomorium songaricum Rupr(Cynomorium)is named as amrita drug,Its resistance is sweet and temperature,which has the functions of reinforcing kidney,strengthening yang,supplementing precision and so on.It has been used as an important anti-aging drugs since ancient times.Early research has shown that the antioxidant fractions of Cynomorium songaricum are mainly enriched in the ethyl acetate and methanol phases,which can be achieved through oxygen free radical scavenging.Our research aimed to investigation the effect of Fraction of Cynomorim songaricum Rupr EtOAc(CSE)on ovariectomzation induced learning and memory disorder in rats and its potential mechanism.1.The effect of CSE on learning and memory in ovariectomized ratsObjective:To investigate the effects of CSE on behaviors in ovariectomized rats.Methods:SD rats(n=60)were randomly divided into normal group,model group,sham operation group,estradiol group,CSE(3.3mg/kg)and CSE(33mg/kg).Alzheimer’s disease model was established by ovariectomization.One week after surgery,estradiol group and CSE groups were intragastrically administered with estradiol and CSE(3.3mg/kg)and CSE(33mg/kg)respectively for 8 consecutive weeks.All groups were measure with Morris water maze and Active avoidance test for successive 6 days.Results:In Morris water maze,Compared with model group,stage of latency was significantly decreased and the times of passing platform was siginificantly increase in CSE(3.3mg/kg)group and CSE(33mg/kg)group.In Active avoidance test,CSE(33mg/kg)group could reduce the numbers of non-response to the conditions and numbers of wrong moves.Conclusion:CSE could improve the learning and memory ability in ovarietomized rat model with Alzheimer’s disease.2.The effect of CSE on acetyl choline(Ach)and concentration of serum hormone(CSH)in ovariectomized miceObjective:To investigate the effects of CSE on Ach and CSH in ovariectomized rats.Methods:It has been described as part 1.After 6 days’ behavioral observation,specimen were collected from the hippocampus area and serum.Hippocampal Ach and serumE2、FSH、LH、T、Cort were measured at 8w post-treatment by radioimmunoassay.Results:Compared with normal group,model group serum Ach level was significantly decrease(p<0.05)(2)CSE(3.3mg/kg)and CSE(33mg/kg)-treated rats the serum were siginificantly decrease in LH,FSH content(p<0.05),but Cort level were markedly increased(p<0.05).Conclusion:CSE can reduce the serum LH levels,so as to enhance and improve the learning and memory function in ovarietomized rat model with Alzheimer’s disease.3.The research of CSE on the brain tissue of ovariectomized ratsObjective:To investigate the effect of CSE on hippocampal neurons.HE staining and ultra-micro perspective electron microscopy were used to observe hippocampal neurons.Results:The neurogical form of pyramidal cells in hippocampus were improved by HE staining.The transmission electronmicroscope(TEM)results showed that CSE-induced mitochondrial swelling and rupture of mitochondrial cristae.Conclusion:CSE could reduce the damage of CA1 pyramidal cells,and helps to maintain the morphology of normal cell.4.The research of CSE in ovariectomized rats in learning and memory mechanismObjective:To study the effect of CSE on the brain tissue of ovariectomized rats and its potential mechanism.Method:It has been described as part 1.Specimen were collected from the hippocampus.P38、p-CREB、SYN、NGF、BDNF、GAP43 expression were teated by Western-blot.Results:The neurological changes of pyramidal cells in CA3 zone of hippocampus were ameliorated,and the expression of GAP-43 and p-CREB were increased significantly(p<0.05).Brain tissue BDNF,SYN,NGF activity were significantly increased(p<0.01)after CSE treatment,respectively.But p38 levels was markedly decreased(p<0.01).Conclusion:CSE could activate the MAPK/CREB pathway,stimulate the expression of the downstream BDNF and NGF,the other is to improve the expression of synaptic protein GAP-43and SYN to protection synaptic structure,both jointly protect neurons.Conclusion:This experiment confirmed Fr.CS-EtOAc could improve learning and memory in ovariectomized rats.On the one hand,Fr.CS-EtOAc could suppressed the content of serum LH,on the other hand,through the activation of MAPK/CREB pathway,downstream BDNF、NGF protein could be improved,both jointing play a role in protecting neurons.Also found that CSE promotes synapse associated protein production of GAP-43 and SYN for protect the synapses.CSE have the same effect as estradiol and show central nervous estrogenic-like effect.