RT Journal Article
SR Electronic
T1 Improved Outcome after Peripheral Nerve Injury in Mice with Increased Levels of Endogenous Omega-3 Polyunsaturated Fatty Acids
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 563
OP 571
DO 10.1523/JNEUROSCI.3371-11.2012
VO 32
IS 2
A1 Gladman, Stacy J.
A1 Huang, Wenlong
A1 Lim, Siew-Na
A1 Dyall, Simon C.
A1 Boddy, Sophie
A1 Kang, Jing X.
A1 Knight, Martin M.
A1 Priestley, John V.
A1 Michael-Titus, Adina T.
YR 2012
UL http://www.jneurosci.org/content/32/2/563.abstract
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 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.