| The question whether or not a state of chronic and moderate ischemia is associated with cognitive alterations, however, has not yet found a definite answer. Human conditions exist that are associated with a state of chronic reduction of cerebral blood flow, such as arteriovenous malformations, carotid stenosis/occlusion, and, perhaps, cerebral small vessels disease.Ginseng, the root of Panax ginseng, is widely used as a tonic medicine throughout the world, and has also been found to be efficacious in the treatment of amnesia. In addition, significant improvement in learning and memory has been observed in brain-damaged rats and aged rats after oral administration of ginseng powder, and the major ginseng saponins, ginsenoside Rb1 and Rg1, are known to improve spatial learning in normal mice.Objective To observe the effect of Panaxadiol , Saponins (PDS)on intellectual decline and cerebral lesion induced by destabilization of cervical vertebra in mice.Methods 40 mice were randomly divided into the normal control group, model group, high PDS doses group, middle and low PDS doses group with 8 animals in each group .The model of destabilization of cervical vertebra was established by injecting 30% lactic acid into the place between the first and the second cervical vertebrae. and three dose of PDS performed on high doses group (28 mg·kg-1),middle dose group (14 mg·kg-1)and low doses group(7 mg·kg-1)which were intragastric once everyday for 100 days .Behaviour of mice was assessed using an ethological approach in a cognitive abilities (water maze tests and step-down experiment). Spontaneous behavior were observed too.100 days later all mice were executed and the activities of acetylcholine esterase (AChE), and the content of acetylcholine (ACh) in encephalon were tested. Pathological change in hippocampus CA1 neurones were examined by HE staining method.The immunohistochemical localization of apoptosis-related protein (bcl-2/bax caspase-3) and beta- amyloid protein (1-40) in mouse brain neurons structure,including the cortex and hippocampus was demonstrated..Results1 Ethology1.1Water mazeSpatial learn and memory ability during acquisition of the task are indicated by swimming full-time and error times. The model groups mice showed a slower learning and memory abilities as compared to the control group mice as indicated by the significant effect of the lactic acid accumulation in the place of cervical vertebra(P<0.01).PDS high dose group showed shorter time in the full-time and lower in error times than the model's(P<0.01)as indicated PDS has certain protective and improving effect on the impaired spatial memory ability and cervical lesion induced by destabilization of cervical vertebra in mice.1.2 Step-down passive avoidanceImpaired long term memory of all the mice were in the step-down passive avoidance task. Latencies to step-down when mice were conditioned were taken as baseline. Retention was tested 24 h after conditioning. the model mice always showed longer latencies and more errors as compared to control mice(P<0.01). PDS high dose group decreased the latency and errors to step-down 24 h after the foot-shock(P<0.01) as indicated PDS has certain protective and improving effect on the impaired long term memory ability. No dose-independent on PDS.1.3 Spontaneous behaviorMice were placed into dark cages 5 minutes before spontaneous behavior was observed on 3 consecutive times. Spontaneous behavior of the model mice were less active than the control'(P<0.01).No difference was detected between the two treatments in their spontaneous behavior in the dark cage, whereas compared to the model groups, an effect of high dose PDS was detected for more active(P<0.01).2. biochemistryCholine acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine ,cholinphospholipid enzyme (AchE) decompounds the neurotransmitter acetylcholine .(ACh) and is a phenotypic marker for cholinergic neurons. Cholinergic neurons in brain are involved in cognitive function, attentional processing and motor control, and changed ChAT/ AchE activity is found in several neurological disorders.The activity of cholinphospholipid enzyme (AchE) of PDS groups were decreased, the content of acetylcholine (Ach) in encephalon was increased, as compared with the model mice. on the contrary,the model group were less active in AchE and more Ach in hippocampus and cerebral cortex than the control group.3. morphology3.1 HE straining of brain tissue: to observe the hippocampus and cerebral cortex, neuronal degeneration, cell necroses karyopycnosis, cell membrane unsharpness and so forth.3.2 Immunohistochemical staining with bax,caspase-3,β-amyloid (1-40): there are more buffy cell than the control in hippocampus and cerebral cortex in the model group than the control'. Protein bcl-2 express to the contrast. PDS high dose prevented the neurons lost and the expression of beta-amyloid protein in mouse brain because of lactic acid accumulation in the place of cervical vertebra,and PDS could restraint appotosis ,which may be related to the genes of bcl-2/bax and caspase3.The hippocampus of mice had a characteristic increase in promote appotosis protein(bax caspase3) and decrease in restraint appotosis protein bcl-2 throughout the CA1region and cerebral cortex.Conclusions:1.The impaired memory abilities and the change of apoptosis-related protein and beta-amyloid protein in mouse brain neurons of the model mice were the result of lactic acid accumulation in the place of cervical vertebra.2. PDS has certain protective and improving effect on the decline of memory ability and cervical lesion induced by destabilization of cervical vertebra in mice.3.The neurons lost and the expression of beta-amyloid protein in mouse brain because of lactic acid accumulation in the place of cervical vertebra were prevented by PDS4. PDS could restraint appotosis , which may be related to the genes of bcl-2/bax and caspase3.
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