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Enriched Endogenous Omega-3 Polyunsaturated Fatty Acids Protect Cortical Neurons from Experimental Ischemic Injury

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Abstract

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential in a variety of neurological disorders, including ischemic stroke. However, the underlying mechanisms still lack investigation. Here, we report that cultured cortical neurons isolated from fat-1 mice with high endogenous n-3 PUFAs were tolerant to oxygen-glucose deprivation/reperfusion (OGD/R) injury. Fat-1 neurons exhibited significantly attenuated reactive oxygen species (ROS) activation induced by OGD/R injury, upregulated antiapoptotic proteins Bcl-2 and Bcl-xL, and reduced cleaved caspase-3. Exogenous administration of docosahexaenoic acid (DHA), a major component of the n-3 PUFA family, resulted in similar protective effects on cultured cortex neurons. We further verified the protective effects of n-3 PUFAs in vivo, using a mini ischemic model with a reproducible cortical infarct and manifest function deficits by occlusion of the distal branch of the middle cerebral artery with focused femtosecond laser pulses. The Fat-1 animals showed decreased ROS expression and higher level of glutathione in the injured brain, associated with improved functional recovery. We therefore provide evidence that n-3 PUFAs exert their protective effects against ischemic injury both in vitro and in vivo, partly through inhibiting ROS activation.

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Acknowledgments

This study was supported by the Macao Science and Technology Development Fund (018/2013/A1), matching grant project MRG003/SHX/2014/ICMS, and multi-year research grant, University of Macau, MYRG122 (Y1-L3)-ICMS12-SHX and MYRG110 (Y1-L2)-ICMS13-SHX. The work was also supported by the “Hundred Talents program,” “Qing Lan Project” of Nanjing Normal University, Jiangsu Provincial Natural Science Foundation (#BK20140917), and National Natural Science Foundation of China (#81501164).

Author Contributions

ZS, HR, CL, XY, PL, CH, TY, and HS designed and performed the study; ZS, HR, CL, JK, JW, TY, and HS analyzed the results; and all authors wrote the draft together and approved the final version.

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Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China

    Zhe Shi, Huixia Ren, Chuanming Luo, Peng Li, Chengwei He, Jian-Bo Wan & Huanxing Su

  2. Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China

    Xiaoli Yao

  3. Laboratory for Lipid Medicine and Technology, the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA

    Jing-X Kang

  4. School of Psychology, Nanjing Normal University, Nanjing, 210097, China

    Ti-Fei Yuan

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  1. Zhe Shi
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  2. Huixia Ren
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  3. Chuanming Luo
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  4. Xiaoli Yao
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Correspondence to Ti-Fei Yuan or Huanxing Su.

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Shi, Z., Ren, H., Luo, C. et al. Enriched Endogenous Omega-3 Polyunsaturated Fatty Acids Protect Cortical Neurons from Experimental Ischemic Injury. Mol Neurobiol 53, 6482–6488 (2016). https://doi.org/10.1007/s12035-015-9554-y

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  • DOI: https://doi.org/10.1007/s12035-015-9554-y

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