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Neurochemical Research

, Volume 40, Issue 6, pp 1102–1110 | Cite as

Nicotinamide Mononucleotide Adenylyltransferase 1 Protects Neural Cells Against Ischemic Injury in Primary Cultured Neuronal Cells and Mouse Brain with Ischemic Stroke Through AMP-Activated Protein Kinase Activation

  • Jia Liang
  • Peng Wang
  • Jia Wei
  • Cuifen Bao
  • Donghe Han
Original Paper

Abstract

Nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) is a nicotinamide adenine dinucleotide biosynthetic enzyme. It has been shown to be neuroprotective against neonatal excitotoxicity-induced brain injury, but its role in ischemic stroke is unclear. In this study, the role of NMNAT1 in oxygen–glucose deprivation (OGD)-induced primary cultured neuronal cell injury and mouse middle cerebral artery occlusion-induced cerebral ischemic injury and its regulation on AMP-activated protein kinase (AMPK) activation were evaluated. The results showed that NMNAT1 overexpression reduced cell death and apoptosis both in vitro and in vivo. Conversely, NMNAT1 knockdown exacerbated cell death and apoptosis. Furthermore, NMNAT1 overexpression regulated neuron survival via AMPK activation, as NMNAT1 overexpression enhanced AMPK activity in OGD-treated cortical neurons, and AMPK inhibitor blocked LV-NMNAT1-induced neuroprotection in OGD-treated cortical neurons. In addition, NMNAT1 overexpression could reduce brain infarction size and improve behavioral outcomes in mice with ischemic stroke. These results suggested that up-regulation of NMNAT1 could induce neuroprotection against ischemic injury through AMPK activation and indicated that NMNAT1 is a potential therapeutic target for stroke.

Keywords

NMNAT1 AMPK Apoptosis Ischemic stroke 

Notes

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (Grant No. 81202783), Foundation of Liaoning Province (No. 2013022030) and the President Foundation of Liaoning Medical University (Grant No. XZJJ20140110). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Conflict of interest

The authors confirm that there are no conflicts.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jia Liang
    • 1
  • Peng Wang
    • 2
  • Jia Wei
    • 1
  • Cuifen Bao
    • 1
  • Donghe Han
    • 2
  1. 1.Key Laboratory of Molecular Cell Biology and New Drug DevelopmentLiaoning Medical UniversityJinzhouPeople’s Republic of China
  2. 2.Key Laboratory of Neurodegenerative Diseases of Liaoning Province and Department of NeurobiologyLiaoning Medical UniversityJinzhouPeople’s Republic of China

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