Objective Estrogen (E2) has a wide neuroprotective effect on central nervous system (CNS) which related to the signaling transduction mediated by estrogen receptor (ER).However, the mechanism of different subtypes of ER involved in the process is still unknown.Recently it was proved that ERα36, a variant of estrogen receptor-α, can respond to both estrogen and anti-estrogen stimuli via activation of the mitogen-activated protein kinase extracellular signal-regulated kinase signaling pathway and promote cell growth.Methods In this study, we detected the expression and distribution of ERα36 in PC12 cells, hippocampal neurons, cortical neurons and glial cells.Then we study the expression pattern of ERα36 in mouse brain of different development stages and the relationship between the brain functions.After that ERα36 gene silencing PC 12 cell model (PC 12-36L) was established.Furthermore, we study the effect of ERα36 low expression on E2 pretreated PC12 apoptosis induced by MPP+ in order to study the effect of ERα36 in membrane initiated estrogen signal pathway in neuron growth and apoptosis and provide a theoretical basis to illustrate the mechanism of membrane initiated estrogen signal pathway in CNS.Results The results shows that: (1) ERα36 was widely expressed in different regions of mouse brain and neuron cells; and increased with age in the cortex; (2) The cell model of ERα36 low expression (PC 12-36L 1) was successfully established by siRNA technology; (3) MPP+ treatment induced apoptosis and inhibit Akt expression but activated P38 protein both PC 12 cell and PC12-36L1 cell.But the survival rate of PC12-36L1 cell was higher than that of PC12 cell; (4) When pretreatment with E2 for 1 h followed by MPP+, the survival rate in ERα36 gene silencing cells is higher than that of in the parental cells.Conclusion It is suggested that ERα36 gene silencing can reduce PC12 apoptosis induced by MPP+ and ERα36 may play an important role in the neuroprotective effect of E2.