The endocannabinoid system is affected by cholesterol dyshomeostasis: Insights from a murine model of Niemann Pick type C disease.

The endocannabinoid system is affected by cholesterol dyshomeostasis: Insights from a murine model of Niemann Pick type C disease. Neurobiol Dis. 2019 Jul 11;:104531 Authors: Oddi S, Caporali P, Dragotto J, Totaro A, Maiolati M, Scipioni L, Angelucci CB, Orsini C, Canterini S, Rapino C, Maccarrone M, Fiorenza MT Abstract The dyshomeostasis of intracellular cholesterol trafficking is typical of the Niemann-Pick type C (NPC) disease, a fatal inherited lysosomal storage disorder presenting with progressive neurodegeneration and visceral organ involvement. In light of the well-established relevance of cholesterol in regulating the endocannabinoid (eCB) system expression and activity, this study was aimed at elucidating whether NPC disease-related cholesterol dyshomeostasis affects the functional status of the brain eCB system. To this end, we exploited a murine model of NPC deficiency for determining changes in the expression and activity of the major molecular components of the eCB signaling, including cannabinoid type-1 and type-2 (CB1 and CB2) receptors, their ligands, N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), along with their main synthesizing/inactivating enzymes. We found a robust alteration of distinct components of the eCB system in various brain regions, including the cortex, hippocampus, striatum and cerebellum, of Npc1-deficient compared to wild-type pre-symptomatic mice. Changes of the eCB component ...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research