Endocannabinoids accumulate in spinal cord of SOD1 G93A transgenic mice.
Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are caused by mutations in the super oxide dismutase 1 (SOD1) gene and transgenic mice for these mutations recapitulate many features of this devastating neurodegenerative disease. Here we show that the amount of anandamide (AEA) and 2-arachidonoylglycerol (2-AG), two endocannabinoids that have neuroprotective properties, increase in spinal cord of SOD1(G93A) transgenic mice. This increase occurs in the lumbar section of spinal cords, the first section to undergo neurodegeneration, and is significant before overt motor impairment. Our results show that chronic neurodegeneration induced by a genetic mutation increases endocannabinoid production possibly as part of an endogenous defense mechanism.
Witting
Anke
A
Department of Pharmacology, University of Washington, Seattle, WA, USA.
Weydt
Patrick
P
Hong
Soyon
S
Kliot
Michel
M
Moller
Thomas
T
Stella
Nephi
N
D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D004195:Disease Models, Animal; D018450:Disease Progression; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D008161:Lumbosacral Region; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000378:metabolism; D053284:Polyunsaturated Alkamides; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics*
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D018696:Neuroprotective Agents; D053284:Polyunsaturated Alkamides; C094503:glyceryl 2-arachidonate; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; C078814:anandamide