The role of PI3K/Akt pathway in BDNF induced expression of synapse relative proteins in primary cultured cortical neurons Wenhua Zheng*, Yan FengXia , Yeliton, Gao Yan, MengChian, Wang Haitao, Wang RiKan, Zhang Lang, and Philip Lazarovici Faculty of Health Science, University of Macau, Macau and State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center, Sun Yat-Sen University, China. *corresponding author. Abstract Normal synapse structure and functions are essential for learning and remembering. BDNF, a major neurotrophic factor member, plays a key role in the development of synapse formation. To reseasrch the role of BDNF in the formation of synapse and its underlying mechanism, we studied the effect of BDNF on the expression of synapse relative proteins synapsin I and synaptotagmin 1(Syr1) in primary cultured cortical neurons. Accordingly, the primary cultured cortical neurons were cultured in serum free condition and treated with various concentration of BDNF. Western blot with antibodies for synapsin I and Syr1 showed that BDNF stimulated the expression of synapsin I and Syr1 in primary cultured cortical neurons. The effect is time- and concentration-dependent with the maximal effect of BDNF at 100 ng/ml and 6 h respectively. Western blot with phospho-antibodis for various kinases showed that BDNF activated the MAPK and the PI3K/Akt pathways in these culture neurons. Blockage of the activation of PI3K/Akt pathway with PI3K specific inhibitor LY294002 attenuated the expression of synapsin I and Syr1 induced by BDNF, in contract, PD98059, a specific MAPK pathway inhibitor has no effect on the expression of these two synapse relative proteins when it was used at the concentration higher enough to block the phosphorylation of MAPK. These results suggest that BDNF is able to induce the expression of synapsin I and Syr1 in primary neurons via the PI3K/Akt pathway. Supported by National Natural Science Fund of China (31371088), Funding from Guangdong Science and Technology Department (No. 2011B050200005). Funding from State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center and SRG at University of Macau.