[Epub ahead of print]
In vitro and in vivo models of Huntington’s disease show alterations in the endocannabinoid system.
Bari M, Battista N, Valenza M, Mastrangelo N, Malaponti M, Catanzaro G, Centonze D, Finazzi-Agrò A, Cattaneo E, Maccarrone M.
Source
Department of Experimental Medicine and Surgery, Tor Vergata University of Rome, 00133, Rome, Italy.
Abstract
In this investigation 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 anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and the activity of their biosynthetic (NAPE-PLD and DAGL, respectively) and hydrolytic enzymes (FAAH and MAGL, respectively), and of their target receptors (CB1, CB2 and TRPV1) in the brain 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 brain of 12-week-old R6/2 mice we found a reduction of NAPE-PLD, DAGL activity and CB binding, mostly associated to changes in striatum and not in cortex, as well as an increase in 2-AG content when compared to 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 non-induced conditions we demonstrated a fully functional ECS. Overall, our data suggest that 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
- PMID:
23659592
[PubMed – as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23659592
