The Expression Of Apoptosis-related Genes, Caspase-3 And NF-κB, In The APPSWE Transgenic Mouse

Alzheimer's disease is a progressive, neurodegenerative central nervous system disease. So far, the incidence and causes of the mechanism unknown, arising more and more attentions from neural scientists and neurology experts. The topic used APPSWE transgenic mice for the study, applying Caspase-3 and NF-κB immunohistochemistry, HE,Nissl staining, RT-PCR and electron microscope and other technical methods. With a view to reveal the roles between the neuroapoptosis and the onset, development of Alzheimer's disease, especially the NF-κB's regulation to neuroapoptosis, to further explore the pathogenesis of AD and provide the basis for clinical treatment.Objective: To investigate the roles between the neuroapoptosis and the onset, development of Alzheimer's disease, especially the NF-κB's regulation to neuroapoptosis, to further explore the pathogenesis of Alzheimer's disease and provide the basis for clinical treatment.Methods: APPSWE transgenic mice from postnatal day 0 to postnatal day 180 were used for the study. HE,Nissl staining, Caspase-3 and NF-κB immunohistochemistry and RT-PCR analysis and other technical methods. HE, Nissl staining observed the structure and morphology of hippocampus; the immunohistochemistry detected the expression of activated Caspase-3 and NF-κB; RT-PCR tested the levels of Caspase-3 mRNA expression.Results: The neuroapoptosis and NF-κB immunostaining in CA3 areas decreased gradually with age increasing. In the meantime, the Caspase-3 positive pyramidal cells and NF-κB positive pyramidal cells were measured. The densities of both caspase-3 and NF-κB positive cells in APPSWE transgenic mice were higher than age-matched controls, and there were statistical differences after P14. In addition, the result of RT-PCR supported the conclusions of immunohistochemistry.Conclusion:1. AD transgenic animal models: the APPSWE positive and pro-generation mice which we have breeded can be used as an ideal model of AD research.2. The relationship between development and the density of pyramidal cells: at P0, the density of pyramidal cells in CA3 area was the highest. With age, the density decreased gradually to P30 stabilizing in the model mice and the control mice. With age increasing, the model mice emerged abnormal nerve cells, electron microscopy showed apoptotic neurons, suggesting that the reduction of cells in AD was achieved through apoptosis.3. The relationship between development and neuroapoptosis: at P0, the density of neuroapoptosis was the highest. With age increasing, the density decreased gradually until stabilized at P30.4. The differences of neuroapoptosis in between the model group and the control group: From P14, the neuroapoptotic in CA3 area of AD model was obviously higher, compared to age-matched controls; in addition, the result of RT-PCR supported the conclusions of Caspase-3 immunohistochemistry, suggesting that the production and development of Alzheimer's disease may be relevant to the neuroapoptosis of developing hippocampus.5. The differences of the NF-κB positive cells in between the model group and the control group: at P0, the density of the NF-κB positive cells was the highest. With age increasing, the density decreased gradually until stabilized at P30.6. The relationship between the activation of NF-κB and Caspase-3 dependent apoptosis: at the same time, the Caspase-3 positive cells and the NF-κB positive cells had correlation, prompting that the onset and development of Alzheimer's disease may be relevant to apoptosis-related genes, Caspase-3 and NF-κB. The action of NF-κB may activate the Caspase-3 expression and neuroapoptosis.