The Effects Of Tenuigenin On Expression Of Neurogranin And PCaMKⅡαin Alzheimer’s Disease Model Rats

BackgroudAlzheimer’s diseases （AD）is a neurodegenerative disease characterized byprogressive learning and memory decline. Its exact mechanism is still unclear. Anumber of studies suggested that the damage of synaptic plasticity, which is closelyrelated to cognitive impairment, participates in the pathological progress of AD. As akind of neural electrophysiological phenomenon, long-term potentiation (LTP)reflects the neuronal synaptic plasticity and represents the mechanism of learning andmemory at cell level. Neurogranin is a neural-specific calmodulin-binding protein aswell as PKC-specific substrate protein which is essential for learning mainly throughthe way of regulating calcium and calmodulin-dependent protein kinases includingcalcium/calmodulin-dependent protein type kinase Ⅱ.Calcium/calmodulin-dependent protein type kinase Ⅱ, known as molecular switchof memory, is the main component of postsynaptic density (PSD). CaMKⅡ alphasubunit is highly expressed in hippocampus and its phosphorylated state at Thr286ispivotal to the induction of LTP. Tenuigenin (TEN), the major component of thepolygala tenuifolia, is benificial for AD patients. But the mechanisms is unclear. Ourprevious studies have already shown that TEN could enhance LTP in hippocampalCA1area. Here, we want to further explore the underlying molecular mechanism.ObjectiveTo investigate the effects of tenuigenin（TEN）on expression of neurogranin(Ng)and phosphorylation of calcium/calmodulin-dependent protein kinase typeⅡ alphasubuint（pCaMKⅡ）in Alzheimer’s disease model rats.Methods60male Wistar rats were divided randomly into four groups：control group，AD model group， low-dose TEN treatment group(12.5mg/ml) and high-dose TENtreatment group(37.5mg/ml). AD model rats were made by injecting ibotenic acidinto Meynert basal nuclei of aging rats induced by D-gal．For low-dose and high-doseTEN treatment groups, equal volume per kilogram weight of12.5mg/ml and37.5mg/ml TEN were respectively administrated by gavage for8weeks.Theexpressions of Ng and pCaMKⅡ in the hippocampus CA1area were measured byimmunohistochemistry method.Results(1) The average absorbance values of Ng and pCaMKⅡ in the hippocampusCA1of the AD model group were decreased significantly（P<0.05） compared withthose of control group，suggesting the expression of Ng and pCaMKⅡ in the ADmodel group was decreased significantly.(2) The average absorbanc values of Ng and pCaMKⅡ in the hippocampusCA1oftwo treatment groups were increased significantly（P<0.05）compared withthose of AD model group, suggesting the expression of Ng and pCaMKⅡ in twotreatment groups were increased significantly.(3) The average absorbance values of Ng and pCaMKⅡ in the hippocampusCA1of the high-dose TEN treatment group(37.5mg/ml) was increased significantlycompared with that of low-dose TEN treatment group(12.5mg/ml)（P<0.05）.Conclusions(1)TEN may increase the expressions of Ng and pCaMKⅡ in the hippocampusCA1area of Alzheimer’s disease model rats.(2)The increasing effect of TEN on expression of Ng and pCaMKⅡ isdose-dependent.