ABSTRACT
Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.
Subject(s)
Animals , Mice , Dopaminergic Neurons/physiology , GABAergic Neurons/physiology , Nucleus Accumbens/metabolism , Reward , Ventral Tegmental Area/metabolismABSTRACT
ObjectiveTo investigate imaging features of the liver, portal vein and hepatic vein or transhepatic inferior venacava in patients with severe liver cirrhosisin multidetector row computed tomography ( MDCT), and assess the feasibility, safety and clinical significance of percutaneous transhepatic intrahepatic portosystemic shunt (PTIPS). MethodsFifty patients with severe liver cirrhosis confirmed by clinical data and imaging examination were enrolled in this study. Simulation of intrahepatic portosystemic shunt by percutaneous transhepatic approch is as follows. The right midaxillary line (the eighth or ninth intercostal space) was selected as puncture point A the right branch of portal vein was puncture point B,transhepatic inferior vena cava was puncture point C, and the distal part of right portal vein was D. A-B-C connection is simulated as percutaneous transhepatic puncture tract, C-B-D connection is simulated as portosystemic shunt tract.After tri-phase contrast-enhanced CT scanning, postprocessing images through multiple planner reconstruction ( MPR ) were obtained. The data were indicated statistically by x ± s. And 95％ confidence interval for mean was calculated.Anatomic relationship among the right portal vein,transhepatic inferior vena cava, hepatic artery and bile duct were analyzed for all patients. ResultsThe length of the needle (A-B-C) is ( 145. 7 ± 14. 8 ) mm. The curvature of the needle ( the angle of A-B line and B-C line) is ( 145.0 ±9.9)°. The length of transhepatic shunt tract (B-C) is (42.7 ±7.2) mm. The length of the shunt tract (C-B-D) is ( 117. 7 ±11.6 ) mm; The angle of the shunt tract ( the angle of B-C line and B-D line) is (1O8.5 ± 5.9)°. In 24/50 patients, transhepatic inferior vena cava locate in the dorsal of the right portal vein, in 26/50 patients they are in the same plane.In all patients, the right branches of hepatic artery and bile duct locate in the ventral of the right portal vein.Conclusion The procedure of PTIPS is feasible and safe. To quantify the length and angle of the needle and the length and angle of the shunt tract provides the anatomic basis for clinical application.