Improved outcome after peripheral nerve injury in mice with increased levels of endogenous omega-3 polyunsaturated fatty acids

Stacy J Gladman, Wenlong Huang, Siew-Na Lim, Simon C Dyall, Sophie Boddy, Jing X Kang, Martin M Knight, John V Priestley, Adina T Michael-Titus

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47 Citations (Scopus)

Abstract

Functional recovery after a peripheral nerve injury (PNI) is often poor. There is a need for therapies that protect neurons against injury and enhance regeneration. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to have therapeutic potential in a variety of neurological disorders, including acute traumatic injury. The objective of this study was to assess the neuroprotective and proregenerative potential of omega-3 PUFAs in PNI. We investigated this in mice that express the fat-1 gene encoding for omega-3 fatty acid desaturase, which leads to an increase in endogenous omega-3 PUFAs and a concomitant decrease in omega-6 PUFAs. Dorsal root ganglion (DRG) neurons from wild-type or fat-1 mice were subjected to a mechanical strain or hypoxic injury, and cell death was assessed using ethidium homodimer-1 labeling. The fat-1 background appears to confer robust neuroprotection against both injuries. We then examined the early functional and morphological changes in wild-type and fat-1 mice after a sciatic nerve crush. An accelerated functional recovery 7 d after injury was seen in fat-1 mice when assessed using von Frey filaments and the sciatic nerve functional index. These observations were also mapped to changes in injury-related markers. The injury-induced expression of ATF-3 was decreased in the DRG of fat-1 mice, whereas the axons detected 6 mm distal to the crush were increased. Fat-1 animals also had some protection against muscle atrophy after injury. In conclusion, both in vitro and in vivo experiments support the idea that a higher endogenous omega-3 PUFA could lead to beneficial effects after a PNI.

Original languageEnglish
Pages (from-to)563-571
Number of pages9
JournalJournal of Neuroscience
Volume32
Issue number2
DOIs
Publication statusPublished - 11 Jan 2012

Keywords

  • spinal-cord-injury
  • activating transcription-factor 3
  • docosahexaenoic acid
  • hippocampal-neurons
  • neurite outgrowth
  • neuroprotectin D1
  • chronic diseases
  • cell-death
  • rat
  • omega-3-fatty-acids

Cite this

Gladman, S. J., Huang, W., Lim, S-N., Dyall, S. C., Boddy, S., Kang, J. X., Knight, M. M., Priestley, J. V., & Michael-Titus, A. T. (2012). Improved outcome after peripheral nerve injury in mice with increased levels of endogenous omega-3 polyunsaturated fatty acids. Journal of Neuroscience, 32(2), 563-571. https://doi.org/10.1523/JNEUROSCI.3371-11.2012