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

Research output: Contribution to journalArticle

37 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

Improved outcome after peripheral nerve injury in mice with increased levels of endogenous omega-3 polyunsaturated fatty acids. / Gladman, Stacy J; Huang, Wenlong; Lim, Siew-Na; Dyall, Simon C; Boddy, Sophie; Kang, Jing X; Knight, Martin M; Priestley, John V; Michael-Titus, Adina T.

In: Journal of Neuroscience, Vol. 32, No. 2, 11.01.2012, p. 563-571.

Research output: Contribution to journalArticle

Gladman, SJ, Huang, W, Lim, S-N, Dyall, SC, Boddy, S, Kang, JX, Knight, MM, Priestley, JV & Michael-Titus, AT 2012, 'Improved outcome after peripheral nerve injury in mice with increased levels of endogenous omega-3 polyunsaturated fatty acids', Journal of Neuroscience, vol. 32, no. 2, pp. 563-571. https://doi.org/10.1523/JNEUROSCI.3371-11.2012
Gladman, Stacy J ; Huang, Wenlong ; Lim, Siew-Na ; Dyall, Simon C ; Boddy, Sophie ; Kang, Jing X ; Knight, Martin M ; Priestley, John V ; Michael-Titus, Adina T. / Improved outcome after peripheral nerve injury in mice with increased levels of endogenous omega-3 polyunsaturated fatty acids. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 2. pp. 563-571.
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AU - Lim, Siew-Na

AU - Dyall, Simon C

AU - Boddy, Sophie

AU - Kang, Jing X

AU - Knight, Martin M

AU - Priestley, John V

AU - Michael-Titus, Adina T

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AB - 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.

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KW - docosahexaenoic acid

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KW - neurite outgrowth

KW - neuroprotectin D1

KW - chronic diseases

KW - cell-death

KW - rat

KW - omega-3-fatty-acids

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