Ng the effects of BdNF in diabetic encephalopathy. Within the present study, BdNF was demonstrated to activate PI3KAkt signaling below high glucose circumstances, because the levels of pAkt and Akt have been elevated. Additionally, BdNF enhanced the mRNA and protein expression levels of Arc, Syn and cREB, all of which can influence synaptic plasticity by means of the PI3KAkt pathway as the effects of BdNF had been inhibited by wortmannin. These findings indicated that BDNFTrkB activates Akt below hyperglycemic situations to reverse the abnormalities in synaptic plasticity and inhibit apoptosis. Taken with each other, these information indicated that BdNF protects hippocampal neurons partially by way of the upregulation of cREB and Arc, that is mediated via the PI3KAkt signaling pathway. Inside the present study, the expression of TrkB was improved following therapy with BdNF below higher glucose circumstances. Though it has been reported that the expression of TrkB is regulated by the cyclic AMPcREB pathway in neurons (51), the administration of PI3K inhibitor did not decrease the expression amount of TrkB, in spite of a reduction in cREB and pAktAkt levels. This suggests that the regulation from the expression of TrkB by BdNF happens upstream of Akt. Of note, BdNF has also been demonstrated to protect retinal neurons from hyperglycemia through the TrkBERKMAPK pathway and attenuate diabetic hyperglycemia via an insulinindependent mechanism in rats (13,29). The regulation of longterm synaptic plasticity and memory formation by Arc are dependent on its phosphorylation by ERK protein, suggesting that MAPK kinases are critical inside the memory method (52). The findings in the present study indicate the possibility of possible interplay amongst the ERKMAPK and PI3KAkt pathways inside the regulation of neuronal plasticity by BdNF. In conclusion, the present study demonstrated that BdNF can activate the PI3KAkt signaling pathway and induce the expressions of synaptic plasticityrelated proteins in hippocampal neurons cultured under higher glucose conditions. This improves synaptic plasticity in the hippocampal neurons and protects them from high glucoseinduced apoptosis. These findings offer a theoretical basis for subsequent investigations around the mechanism of BdNFmediated hippocampal neuroprotection. Moreover, the present study provides novel insights into therapeutically targeting BdNF and PI3KAkt signaling for the prevention of diabetic encephalopathy.ZHONG et al: NEUROPROTEcTIVE Effect OF BdNF ON HIPPOcAMPAL NEURONSAcknowledgements Not applicable. Funding The present study was funded by the Shanghai Sixth People’s Hospital Group Science Foundation, the Shanghai Science and Technology commission Foundation Analysis Project (grant no. 13Jc1401504) and also the chinese Activators and Inhibitors products National Organic Science Foundation (grant no. T3ss Inhibitors medchemexpress 81300933). Availability of data and components The datasets made use of andor analyzed throughout the present study are obtainable from the corresponding author on affordable request. Authors’ contributions YZ, YM and YTZ performed the experiments, have been involved in information collection and drafted the manuscript. TH and QL performed the statistical analyses and have been involved in study design and style. WL assisted in drafting the manuscript. All authors study and approved the final manuscript. Ethics approval and consent to participate All animal experiments had been performed in accordance with the National Institutes of Wellness Recommendations for the care and Use of Laboratory Animals and authorized by the Ethics committee of A.