Open Access

Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression

  • Authors:
    • Xue‑Shan Zhao
    • Qi Wu
    • Juan Peng
    • Li‑Hong Pan
    • Zhong Ren
    • Hui‑Ting Liu
    • Zhi‑Sheng Jiang
    • Gui‑Xue Wang
    • Zhi‑Han Tang
    • Lu‑Shan Liu
  • View Affiliations

  • Published online on: December 16, 2016     https://doi.org/10.3892/mmr.2016.6055
  • Pages: 712-718
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hyperlipidemia is a risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a lipid regulatory gene involved in cell apoptosis. However, the function and mechanism of PCSK9 in neuronal apoptosis following hyperlipidemia remains to be elucidated. The present study established a hyperlipidemic mouse model by feeding a high‑fat diet (HFD) to 6‑week‑old apoE(‑/‑) mice. Plasma lipid levels, hippocampal lipid accumulation, hippocampal histology, and hippocampal neuronal apoptosis were all monitored for changes. The expression levels of PCSK9, β‑secretase 1 (BACE1), B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), and caspase‑3 in hippocampal CA3 and CA1 neurons were also measured. Results demonstrated that a HFD increased the lipid accumulation in the CA3 hippocampus and the levels of plasma lipids, including triglycerides, total cholesterol, low‑density lipoprotein, and high‑density lipoprotein. In addition, CA3 neurons in the HFD group indicated apparent injuries and increased neuronal apoptosis, which are associated with the expression of Bcl‑2, Bax, and caspase‑3. A HFD also increased the expression levels of PCSK9 and BACE1. BACE1 promotes cleavage of amyloid precursor proteins to generate β‑amyloid peptide (Aβ), which induces neuronal apoptosis. Protein levels of Aβ are associated with the observation of amyloid plaques in the hippocampus of the HFD group. The results suggest that hyperlipidemia regulates neuronal apoptosis by increasing PCSK9 and BACE1 expression. Overall, the current study may elucidate the role of lipid metabolism disorder in AD pathogenesis.
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February-2017
Volume 15 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhao XS, Wu Q, Peng J, Pan LH, Ren Z, Liu HT, Jiang ZS, Wang GX, Tang ZH, Liu LS, Liu LS, et al: Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression. Mol Med Rep 15: 712-718, 2017
APA
Zhao, X., Wu, Q., Peng, J., Pan, L., Ren, Z., Liu, H. ... Liu, L. (2017). Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression. Molecular Medicine Reports, 15, 712-718. https://doi.org/10.3892/mmr.2016.6055
MLA
Zhao, X., Wu, Q., Peng, J., Pan, L., Ren, Z., Liu, H., Jiang, Z., Wang, G., Tang, Z., Liu, L."Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression". Molecular Medicine Reports 15.2 (2017): 712-718.
Chicago
Zhao, X., Wu, Q., Peng, J., Pan, L., Ren, Z., Liu, H., Jiang, Z., Wang, G., Tang, Z., Liu, L."Hyperlipidemia-induced apoptosis of hippocampal neurons in apoE(-/-) mice may be associated with increased PCSK9 expression". Molecular Medicine Reports 15, no. 2 (2017): 712-718. https://doi.org/10.3892/mmr.2016.6055