TY - JOUR
T1 - In vitro and in vivo models of Huntington's disease show alterations in the endocannabinoid system
AU - Bari, Monica
AU - Battista, Natalia
AU - Valenza, Marta
AU - Mastrangelo, Nicolina
AU - Malaponti, Marinella
AU - Catanzaro, Giuseppina
AU - Centonze, Diego
AU - Finazzi-Agrò, Alessandro
AU - Cattaneo, Elena
AU - Maccarrone, Mauro
PY - 2013/7
Y1 - 2013/7
N2 - In this study, we analyzed the components of the endocannabinoid system (ECS) in R6/2 mice, a widely used model of Huntington's disease (HD). We measured the endogenous content of N-arachidonoylethanolamine and 2-arachidonoylglycerol and the activity of their biosynthetic enzymes (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D and diacylglycerol lipase, respectively) and hydrolytic enzymes [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively] and of their target receptors (type 1 cannabinoid receptor, type 2 cannabinoid receptor, and transient receptor potential vanilloid-1) in the brains of wild-type and R6/2 mice of different ages, as well as in the striatum and cortex of 12-week-old animals. In addition, we measured FAAH activity in lymphocytes of R6/2 mice. In the whole brains of 12-week-old R6/2 mice, we found reductions in N-acyl-phosphatidylethanolamine- hydrolyzing phospholipase D activity, diacylglycerol lipase activity and cannabinoid receptor binding, mostly associated with changes in the striatum but not in the cortex, as well as an increase in 2-arachidonoylglycerol content as compared with wild-type littermates, without any other change in ECS elements. Then, our analysis was extended to HD43 cells, an inducible cellular model of HD derived from rat ST14A cells. In both induced and noninduced conditions, we demonstrated a fully functional ECS. Overall, our data suggest that the ECS is differently affected in mouse and human HD, and that HD43 cells are suitable for high-throughput screening of FAAH-oriented drugs affecting HD progression. We analyzed the endocannabinoid system (ECS) in the brain of wild-type and R6/2 mice, a model of Huntington's disease (HD). In addition, we characterized the ECS in HD43 cells, an inducible model of HD. Our data suggest that ECS is differently affected in mouse and human HD, and that HD43 cells are suitable for the screening of ECS-oriented drugs against HD progression.
AB - In this study, we analyzed the components of the endocannabinoid system (ECS) in R6/2 mice, a widely used model of Huntington's disease (HD). We measured the endogenous content of N-arachidonoylethanolamine and 2-arachidonoylglycerol and the activity of their biosynthetic enzymes (N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D and diacylglycerol lipase, respectively) and hydrolytic enzymes [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase, respectively] and of their target receptors (type 1 cannabinoid receptor, type 2 cannabinoid receptor, and transient receptor potential vanilloid-1) in the brains of wild-type and R6/2 mice of different ages, as well as in the striatum and cortex of 12-week-old animals. In addition, we measured FAAH activity in lymphocytes of R6/2 mice. In the whole brains of 12-week-old R6/2 mice, we found reductions in N-acyl-phosphatidylethanolamine- hydrolyzing phospholipase D activity, diacylglycerol lipase activity and cannabinoid receptor binding, mostly associated with changes in the striatum but not in the cortex, as well as an increase in 2-arachidonoylglycerol content as compared with wild-type littermates, without any other change in ECS elements. Then, our analysis was extended to HD43 cells, an inducible cellular model of HD derived from rat ST14A cells. In both induced and noninduced conditions, we demonstrated a fully functional ECS. Overall, our data suggest that the ECS is differently affected in mouse and human HD, and that HD43 cells are suitable for high-throughput screening of FAAH-oriented drugs affecting HD progression. We analyzed the endocannabinoid system (ECS) in the brain of wild-type and R6/2 mice, a model of Huntington's disease (HD). In addition, we characterized the ECS in HD43 cells, an inducible model of HD. Our data suggest that ECS is differently affected in mouse and human HD, and that HD43 cells are suitable for the screening of ECS-oriented drugs against HD progression.
KW - endocannabinoid
KW - fatty acid amide hydrolase (FAAH)
KW - Huntington's disease
KW - lymphocyte
KW - R6/2 mice
UR - http://www.scopus.com/inward/record.url?scp=84879990830&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84879990830&partnerID=8YFLogxK
U2 - 10.1111/febs.12329
DO - 10.1111/febs.12329
M3 - Article
C2 - 23659592
AN - SCOPUS:84879990830
VL - 280
SP - 3376
EP - 3388
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 14
ER -