The Protective Effect And The Morphological Research Of ZBPY Decoction To Dendritic Spines In A Model Of Both Alzheimer's Disease And Spleen Yin Deficiency Syndrome

Objective: Alzheimer's disease (AD) is the most common of neurodegenerative disorder in the central nervous system. Clinically the disease results in impairment of memory, cognition and behavior. Histopathologically, AD is characterized by the presence of increased numbers of neurofibrillary tangles (NFT), amyloid containing senile plaques(SP) , synapse loss and dysfunction. The decline of cognition correlates with the synapse loss and dysfunction in hippocampus and cortex. The majority of excitatory synaptic connections in the central nervous system are located on small dendritic protrusions called dendritic spines. Spines are enriched in signaling molecules and critical to the majority of exciting synaptic transmission to neuron in the brain. It involves in the synaptic plasticity and learning. The changes in spine morphology and number may affect the efficiency of electrical and biochemical signal transduction of synaptic inputs, then potentially influencing learning and memory. The hippocampus is critical for the encoding, storage, consolidation and reparation of memory. The regions of CA1, CA3, DG in hippocampus has intimate relationship with the learning and memory. The synapse loss in hippocampus and cortex is severe phenomenon of AD. The synapse loss means the loss of dendritic spines and nervous information. The decline of dendritic spine density in AD correlates with the dysfunction of learning and memory. The Spleen Yin Deficiency Syndrome is one syndrome of mental retardation. The Zi-Bu-Pi-Yin Decoction can cure theSpleen Yin Deficiency Syndrome. The previous studies of our group suggested that the Zi-Bu-Pi-Yin Decoction has the function of anti-oxidation and improving the ability of learning and memory. ZBPY decoction has the notable protective role of the neurons. Therefore we want to know the relation between the morphological changes of dendritic spines and the AD model of the integrated disease and syndrome. And we observed the changes after the treatment of ZBPY decoction. Finally the research is the neuroanatomical basis for the morphological changes of dendritic spines in a Model of both Alzheimer's Disease and Spleen Yin Deficiency Syndrome and the neuroprotective effect of ZBPY decoction.Methods: Rat model of Spleen Yin Deficiency Syndrome was set up by the classical method. The classical method involves the eating and drinking without temperance, overfatigue and consumption of Yin decoction. Then the incubated Aβ1-40 was injected into the bilateral hippocampus of each rat and cured by the ZBPY Decoction. The behavioral abnormalities were investigated by step-down test and Morris water maze test. Observe the changes of learning and memory. After perfusion, we observed the dendritic spine density in hippocampus (CA1,CA3,DG) and cortex with the method of Golgi stain.Result: 1.The two model groups of Spleen yin deficiency had the appearance of Yin deficiency leading to endogenous heat ,for example that increase in drinking water, objective elevation of the body temperature. The ability of learning and memory of the two AD groups was reduced conspicuously. The symptom of yin deficiency and abnormal behavior of the ZBPY group were improved in AD rat model.2. The density of dendritic spine in the Model of both Alzheimer's Disease and Spleen Yin Deficiency Syndrome is less than the Model of Spleen Yin Deficiency Syndrome; The density of dendritic spine in the Model of the ZBPY Decoction is more than the other AD groups; The density of dendritic spine in the Model of AD is less than the control group.Conclusions: 1.Try to improve the methods to make the models in this experiment and then the changes of behavior and symptom were observed in syndrome, disease, and combined syndrome with disease. ZBPY improved the symptom of spleen yin deficiency and dysfunction of learning andmemory in AD rat combined with Spleen yin deficiency.2.The neuroprotective effect of the ZBPY Decoction is correlated with the maintain of dendritic spine's density. The results are the morphological basis of the neuroprotective mechanism of the ZBPY Decoction.