Changes Of Dendritic Spines And Synapses In The Process Of Brain Development In APP/PS1 Mice

Alzheimer disease is a kind of degenerative diseases of central nervous system with the main clinical features of memory loss, cognitive impairment, life ability to drop and mental abnormalities, and can cause significant damage in the central nervous system. With the increasing incidence, it has been becoming a world problem because it has seriously affected the health and normal life of the elderly and caused significant economic burden to family and society. However, the mechanism of AD is still unclear. Communication between neurons occurs mainly in the synapse, and synaptic loss and synaptic dysfunction is widely considered to be the mechanism of cognitive impairment in AD. As the main part of the postsynaptic, dendritic spines are the major postsynaptic sites of excitatory neurotransmission and play a special role in neurotransmission because of their unique structure. The importance of dendritic spines can be further emphasized if we consider the fact that many diseases that result in cognitive deficits or abnormalities such as Down’s syndrome, Fragile X syndrome and epilepsy produce abnormalities in dendritic spine morphology or spine number. Therefore, dendritic spines are critical structures and play an important role in maintaining normal function of the central nervous system. In addition, the study on dendritic spines has been becoming the focus in AD. There is a significant loss of dendritic spines and dendritic degeneration in brains of AD patients. But in the process of pathogenesis, how the morphology of dendritic spines change with the β-Amyloid accumulation has not been reported domestie and foreign literatures. DiI diotistic, immunohistochemistry and electron microscopy were used to analyze the problems how dendritic spines and synapses change in two groups of mice with age of P0-P12 m. The study will provide valuable basis and important reference data for the causes of cognitive impairment and drug targets to dendritic spines and synapses in AD.Objective: Our aim is to study the changes of dendritic spines and synapses in the process of brain development in APP/PS1 mouse and try to clarify the relationship between age-dependent pathogenesis dendritic spines and synapse and Aβ accumulation.Methods: APP/PS1 transgenic mice from postnatal day 0 to postnatal day 360 were used as Alzheimer’s disease(AD) model. DiI diotistic, Immunohistochemistry and Transmission electron microscopy were carried out analyze the changes in brain tissue.Results: Amyloid plaques were observed from P6 m in APP/PS1 mice. From P3 m, the length and density of dendritic spines in CA1 area of APP/PS1 mice were significantly lower in wild type mice(P<0.01 or P<0.05). Immunohistochemistry result showed that the density of synaptophysin from P3 m were reduced in APP/PS1 mice(P<0.01 or P<0.05).Conclusion: APP/PS1 mice grew up with the progressive morphology changes of dendritic spine and the number decrease of dendritic spines and synapses. Degeneration of dendritic spines and synapses is the early feature of AD, and the loss of dendritic spines and synapses, which may be caused by soluble Aβ oligomer toxicity appeared earlier than the formation of amyloid plaques. The loss of dendritic spine directly associated with AD incidence was a good index for evaluating the progress of the disease. Therefore, dendritic spines and synapses could be used as the important target of the clinical intervention and drug development early.