ABSTRACT
Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP2, and PIP3. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.
Subject(s)
Carrier Proteins/metabolism , Cocaine/pharmacology , Nucleus Accumbens/drug effects , Receptors, AMPA/metabolism , TOR Serine-Threonine Kinases/metabolism , Animals , Biotinylation , Blotting, Western , Central Nervous System Sensitization/drug effects , Male , Mice , Mice, Inbred C57BL , Motor Activity/drug effects , Nucleus Accumbens/metabolismABSTRACT
OBJECTIVE: To investigate the relationship between condylar marrow signal abnormalities and temporomandibular joint internal derangement (TMJID). METHODS: Oblique sagittal T1 weighted MR imaging at closed and open mouth and Oblique sagittal T2 weighted MR imaging at closed mouth were obtained from 88 joints of 44 patients suffering from TMD. Condylar marrow signal abnormalities were reviewed and classified into bone marrow edema pattern (hypointense T1, hyperintense T2), sclerosis pattern (hypointense T1 and hypointense T2) and combined edema and sclerosis pattern. RESULTS: Of 88 joints, 13 (14.8%) joints showed condylar marrow signal abnomalities, among which 11 belonged to edema pattern and, 1 was sclerosis pattern and the other was the combined patten. Of 13 joints with condylar marrow signal abnomalities, 11 (84.6%) had TMJID. Of 75 joints with normal marrow signal, 25 (33.3%) joints had TMJID. There was significant correlation between condylar marrow signal abnormalities and TMJID (P < 0.05). CONCLUSION: Disc displacement is one of the factors inducing condylar marrow signal abnormalities. The pathological process from disc displacement to osteonecrosis requires further study.
Subject(s)
Magnetic Resonance Imaging , Mandibular Condyle/pathology , Temporomandibular Joint Disorders/diagnosis , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Temporomandibular Joint Disc/pathology , Temporomandibular Joint Disorders/pathologyABSTRACT
PURPOSE: To investigate the relationship between condylar marrow signal abnormalities and joint pain. METHODS: Oblique sagittal T1 and T2 weighted MR imaging at closed mouth was obtained from 88 joints of 44 patients who complained of unilateral TMJ pain. The condylar marrow signal of pain-free side served as self-control. All patients rated their pain levels by a visual analogue scale (VAS). RESULTS: Of 44 painful joints, 11(25% joints showed condylar marrow signal abnormalities, all of which were edema pattern. While there had condylar marrow signal abnormalities only in 2 (4.5%) of 44 pain-free TMJs. There was significant correlation between joint pain and condylar marrow signal abnormalities (P<0.01). The VAS score of patients with and without condylar marrow signal abnormalities was respectively 39.5+/-27.5 and 42.6+/-21.9, There was no correlation between them (P=0.696). CONCLUSION: Temporomandibular joint pain is closely correlated with condylar marrow signal abnormalities, but the pain degree has no association with it.
