Ng the effects of BdNF in diabetic encephalopathy. Within the present study, BdNF was demonstrated to activate PI3KAkt signaling beneath higher glucose conditions, as the levels of pAkt and Akt have been elevated. CD34 Inhibitors products Furthermore, 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 Carbazochrome pathway as the effects of BdNF were inhibited by wortmannin. These findings indicated that BDNFTrkB activates Akt under hyperglycemic conditions to reverse the abnormalities in synaptic plasticity and inhibit apoptosis. Taken together, these data indicated that BdNF protects hippocampal neurons partially by means of the upregulation of cREB and Arc, which can be mediated by way of the PI3KAkt signaling pathway. Within the present study, the expression of TrkB was enhanced following remedy with BdNF under high glucose conditions. Although it has been reported that the expression of TrkB is regulated by the cyclic AMPcREB pathway in neurons (51), the administration of PI3K inhibitor didn’t lower the expression amount of TrkB, regardless of a reduction in cREB and pAktAkt levels. This suggests that the regulation of the expression of TrkB by BdNF occurs upstream of Akt. Of note, BdNF has also been demonstrated to safeguard retinal neurons from hyperglycemia via 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 crucial within the memory process (52). The findings from the present study indicate the possibility of prospective interplay amongst the ERKMAPK and PI3KAkt pathways in 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 below higher glucose conditions. This improves synaptic plasticity within the hippocampal neurons and protects them from high glucoseinduced apoptosis. These findings present a theoretical basis for subsequent investigations on the mechanism of BdNFmediated hippocampal neuroprotection. Furthermore, 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 Study Project (grant no. 13Jc1401504) and the chinese National All-natural Science Foundation (grant no. 81300933). Availability of data and supplies The datasets utilised andor analyzed in the course of the present study are readily available from the corresponding author on reasonable request. Authors’ contributions YZ, YM and YTZ performed the experiments, had been involved in information collection and drafted the manuscript. TH and QL performed the statistical analyses and have been involved in study design. WL assisted in drafting the manuscript. All authors read and authorized the final manuscript. Ethics approval and consent to participate All animal experiments had been performed in accordance using the National Institutes of Well being Suggestions for the care and Use of Laboratory Animals and authorized by the Ethics committee of A.