title: Improved outcome after peripheral nerve injury in mice with increased levels of endogenous ω-3 polyunsaturated fatty acids.
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. ω-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 pro-regenerative potential of ω-3 PUFAs in PNI. We investigated this in mice that express the fat-1 gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-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 ω-3 PUFA could lead to beneficial effects after a PNI.
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK. s.gladman@qmul.ac.uk
authors.forename: Stacy J
authors.initials: SJ
authors.lastname: Gladman
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.forename: Siew-Na
authors.initials: SN
authors.lastname: Lim
authors.forename: Simon C
authors.initials: SC
authors.lastname: Dyall
authors.forename: Sophie
authors.initials: S
authors.lastname: Boddy
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.forename: Martin M
authors.initials: MM
authors.lastname: Knight
authors.forename: John V
authors.initials: JV
authors.lastname: Priestley
authors.forename: Adina T
authors.initials: AT
authors.lastname: Michael-Titus
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018696:Neuroprotective Agents / Q000097:blood / Q000494:pharmacology*; D059348:Peripheral Nerve Injuries / Q000178:diet therapy* / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D015820:Cadherins; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D018696:Neuroprotective Agents; C502406:fat1 protein, mouse