Brain-derived neurotrophic factor inhibits hyperglycemia-induced apoptosis and downregulation of synaptic plasticity-related proteins in hippocampal neurons via the PI3K/Akt pathway

Zhong,Yuan; Zhu,Yitong; He,Ting; Li,Wei; Li,Qinjie; Miao,Ya

doi:10.3892/ijmm.2018.3933

Brain-derived neurotrophic factor inhibits hyperglycemia-induced apoptosis and downregulation of synaptic plasticity-related proteins in hippocampal neurons via the PI3K/Akt pathway

Authors:
- Yuan Zhong
- Yitong Zhu
- Ting He
- Wei Li
- Qinjie Li
- Ya Miao
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Affiliations: Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China
Published online on: October 15, 2018 https://doi.org/10.3892/ijmm.2018.3933
Pages: 294-304
Copyright: © Zhong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

It is not known whether brain‑derived neurotrophic factor (BDNF) protects hippocampal neurons from high glucose‑induced apoptosis and/or synaptic plasticity dysfunction. The present study aimed to assess whether BDNF exerted a neuroprotective effect in rat hippocampal neurons exposed to high glucose and examine the underlying mechanisms. The apoptosis of primary hippocampal neurons was assessed by Annexin V‑fluorescein isothiocyanate/propidium iodide staining. The mRNA and protein expression levels were measured by reverse transcription‑quantitative polymerase chain reaction and western blot experiments, respectively. Synaptic plasticity was evaluated by the immunolocalization of synaptophysin (Syn). Exposure of the hippocampal neurons to high glucose (75 mM for 72 h) resulted in cell apoptosis, decreased mRNA and protein expression levels of three synaptic plasticity‑related proteins (Syn, Arc and cyclic AMP response element‑binding protein), and changes in the cellular distribution of Syn, indicating loss of synaptic density. These effects of high glucose were partially or completely reversed by prior administration of BDNF (50 ng/ml for 24 h). Pre‑treatment with wortmannin, a phosphatidylinositol‑3‑kinase (PI3K) inhibitor, suppressed the ability of BDNF to inhibit the effects of high glucose. In addition, BDNF significantly upregulated the tropomyosin‑related kinase B, its cognate receptor, Akt and phosphorylated Akt at the protein levels under high glucose conditions. In conclusion, high glucose induced apoptosis and downregulated synaptic plasticity‑related proteins in hippocampal neurons. These effects were reversed by BDNF via the PI3K/Akt signaling pathway.

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