Research On The Mechanism Of RBM8A Affecting The Behavior Of APP/PS1 Mice

Background/ObjectiveWith Chinese population ages,the prevalence of Alzheimer's disease is increasing.Alzheimer's disease is a slowly progressing neurodegenerative degenerative disease that initially manifests as memory loss,then gradually progresses to severely impaired executive and cognitive functions,and eventually loses the ability to live independently As clinical trials of Alzheimer's disease have been declared unsuccessful,research and treatment of the disease have entered a confused period.Promoting the repair of brain tissue morphology and function by promoting neuron regeneration is an important exploration approach and a new breakthrough.We have discovered an exon junction complex factor RBM8A through the whole genome RNAi Screen,which is involved in the functions of RNA splicing,transport,degradation and translation;plays a vital role in the cell division cycle and cell survival process;participates and maintain Proliferation of neuronal precursor cells.We hope that by over-expressing RBM8A in the subgranular region of the hippocampal dentate gyrus of APP/PS1 mice,it will promote the regeneration of neurons in this region,and affect the function of mouse brain tissues,thus affecting the behavior of APP/PS1 mice.Providing a basis for in-depth study of neuronal regeneration to improve the symptoms of Alzheimer's disease.MethodWe used the mouse as a model organism for studying.qPCR and Western-blot experiments were used to study the differences in the expression of RBM8A in mice at different ages and the differences in the expression of RBM8A in APP/PS1 mice and wild-type mice.The over-expressing RBM8A and control AAV virus were constructed,and the virus were injected into the hippocampal dentate gyrus region of APP/PS1 mice using brain stereotactic injection.The immunofluorescence and laser confocal imaging were used to observe the neuron regeneration in the hippocampal dentate gyrus region.The behavioral differences of APP/PS 1 mice and wild-type mice in the over-expressed RBM8A group and the control group were observed through animal behavioral experiments of Contextual Fear Conditioning.ResultsThe results showed that the expression of RBM8A will gradually decrease with the increase of mouse age.There is a statistically significant difference in expression between I month and 12 months(P<0.05).And the expression of RBM8A in APP/PS1 mice was lower than wild-type mice in the same age(P<0.05).After over-expression of RBM8A in the dentate gyrus of APP/PS1 mice,Ki67-positive and DCX-positive cells in the subgranular region of the dentate gyrus significantly increased compared with the control group(P<0.01);The cell ratio between the number of double-positive cells Ki67 and EGFP and the total EGFP positive cells was increased compared with the control group(P<0.01);the ratio of the number of DCX and EGFP double positive cells to the total EGFP positive cells was increased compared with the control group(P<0.01).The results of Contextual Fear Conditioning behavior experiments found that over-expressing RBM8A APP/PS 1 mice,the ability to learn fear was significantly higher than the control group,that is,the panic index was significantly higher than the control group(P<0.05),and reached same level of the normal wild-type mice.ConclusionIn summary,with the mouse age increases,the neural progenitor cell proliferation ability decreases,and APP/PS1 mice have lower neuron cell proliferation ability than wild type mice in the same age.In APP/PS1 mice,overexpression of RBM8A can promote the proliferation of neuronal cells,and can change the behavioral phenotype of mice to a certain extent.This study provides important clues for neuronal regeneration in Alzheimer's disease and provides possibilities for further exploration of ways to alleviate the symptoms of Alzheimer's disease.