Molecular Mechanism Of BRD2 Defect On Neural Cell Function

Bromodomain containing 2(BRD2)gene is highly expressed in the de’veloping nervous system.Past studies have found that BRD2 gene mutations are associated with central nervous system disease(e.g.,idiopathic epilepsy),and related studies have shown that Brd2(mouse)is essential for embryogenesis and neural tube closure.However,the role of BRD2 in the human nervous system is still lacking in molecular mechanisms study.The content of this research is to differentiation of human embryonic stem cells into neurons,and to explore the effects of BRD2 on human neurons and astrocytes.Objective:To study the effect of BRD2 on human nerval cells including Glutamatergic neurons,GABAergic neurons and astrocytes.Method:The siRNA was used to knock down the expression of BRD2 at the period of differentiating human embryonic stem cells into Gluta matergic neuron and GABAergic neuron.Then observed the effect on neuron growth.Since BRD2 is associated with immunity,we also used siRNA to knock down the expression of BRD2 in human astrocyte in order to detect the level change of inflammatory cytokine secreted by astrocytes.Result:After knockdown of BRD2 expression,human glutamatergic neurons and GABAergic neurons have neurite growth disorders,and human glial inflammatory cytokine expression is reduced.Conclusion:Lacking of BRD2 in development leads to human glutamatergic neurons and GABAergic neuron neurite outgrowth disorder,which could affect the structure and function of neural networks,possibly as a central nervous system diseases basis.At the same time,the expression of immune factors expressed by human astrocytes will also change,which is related to central nervous system inflammation,which can affect the function of neurons and even lead to neuronal death.