Activation of Group I Metabotropic Glutamate Receptors Increases Serine Phosphorylation of GluR1 ␣-Amino-3- hydroxy-5-methylisoxazole-4-propionic Acid Receptors in the Rat Dorsal Striatum

ABSTRACT Protein phosphorylation is an important mechanism for the post-translational modulation of ionotropic glutamate receptors. In this study, we investigated the regulation of ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1 subunit phosphorylation by the stimulation of group I metabotropic glutamate receptors (mGluRs) in the rat dorsal striatum in vivo. Stimulation of group I mGluRs was found to increase GluR1 phosphorylation of Ser831 and Ser845 in phospholipase C (PLC)-coupled Ca 2ϩ cascades. Interactions of protein kinases activated by intracellular Ca 2ϩ release downstream to PLC modulate the phosphorylation state of GluR1 on Ser831 and Ser845: phosphorylation of GluR1 on Ser831 is up-regulated by the protein kinase C and calcium-calmodulin-dependent protein kinase (CaMK)/c-Jun N-terminal kinase (JNK) pathways, whereas phosphorylation of GluR1 on Ser845 is up-regulated by the protein kinase A (PKA), PKA/ERK1/2, and PKA/JNK pathways. The phosphorylation state of GluR1 on Ser831 and Ser845 and the activity of protein kinases are further regulated by protein phosphatases. These data suggest that GluR1 phosphorylation of Ser831 and Ser845 via stimulation of group I mGluRs is regulated by the interactions of PLC-coupled protein kinases and protein phosphatases in the dorsal striatum. Group I metabotropic glutamate receptors (mGluRs) (mGluR1/5) are densely expressed in the striatum and are colocalized with the majority of either striatonigral or striatopallidal neuron

Fulminant myocarditis managed with pulsatile extracorporeal life support; use of Twin Pulse Life support (T-PLS®)

Fulminant myocarditis frequently results in severe hemodynamic deterioration. High-dose vasopressors or sometimes mechanical circulatory support are required. We report on two cases of fulminant myocarditis successfully treated with pulsatile extracorporeal life support (T-PLS®, Twin Pulse Life support, New heart bio.BHK, Seoul, Korea). With T-PLS, we were able to provide mechanical support to patients until they recovered completely

Impact of commercial cigarette smoke condensate on brain tissue co-cultured with astrocytes and blood-brain barrier endothelial cells

The purpose of the current study was to investigate the effect of two commercial cigarette smoke condensates (CCSC) on oxidative stress and cell cytotoxicity in human brain (T98G) or astrocytes (U-373 MG) in the presence of human brain microvascular endothelial cells (HBMEC). Cell viability of mono-culture of T98G or U-373 MG was markedly decreased in a concentration-dependent manner, and T98G was more susceptible than U-373 MG to CCSC exposure. Cytotoxicity was less prominent when T98G was co-cultured with HBMEC than when T98G was co-cultured with U-373 MG. Significant reduction in trans-epithelial electric resistance (TEER), a biomarker of cellular integrity was noted in HBMEC co-cultured with T98G (HBMEC-T98G co-culture) and U-373 MG co-cultured with T98G (U-373 MG-T98G co-culture) after 24 or 48 hr CCSC exposure, respectively. TEER value of U-373 MG co-cultured with T98G (79-84%) was higher than HBMEC co-cultured with T98G (62-63%) within 120-hr incubation with CCSC. Reactive oxygen species (ROS) generated by CCSC in mono-culture of T98G and U-373 MG reached highest levels at 4 and 16 mg/ml, respectively. ROS production by T98G fell when co-cultured with HBMEC or U-373MG. These findings suggest that adverse consequences of CCSC treatment on brain cells may be protected by blood-brain barrier or astrocytes, but with chronic exposure toxicity may be worsened due to destruction of cellular integrity.

Post-Translational Modification Biology of Glutamate Receptors and Drug Addiction

Post-translational covalent modifications of glutamate receptors remain a hot topic. Early studies have established that this family of receptors, including almost all ionotropic and metabotropic glutamate receptor subtypes, undergoes active phosphorylation at serine, threonine, or tyrosine residues in their intracellular domains. Recent evidence identifies several glutamate receptor subtypes to be direct substrates for palmitoylation at cysteine residues. Other modifications such as ubiquitination and sumoylation at lysine residues also occur to certain glutamate receptors. These modifications are dynamic and reversible in nature and are regulatable by changing synaptic inputs. The regulated modifications significantly impact the receptor in many ways, including interrelated changes in biochemistry (synthesis, subunit assembling, and protein–protein interactions), subcellular redistribution (trafficking, endocytosis, synaptic delivery, and clustering), and physiology, usually associated with changes in synaptic plasticity. Glutamate receptors are enriched in the striatum and cooperate closely with dopamine to regulate striatal signaling. Emerging evidence shows that modification processes of striatal glutamate receptors are sensitive to addictive drugs, such as psychostimulants (cocaine and amphetamine). Altered modifications are believed to be directly linked to enduring receptor/synaptic plasticity and drug-seeking. This review summarizes several major types of modifications of glutamate receptors and analyzes the role of these modifications in striatal signaling and in the pathogenesis of psychostimulant addiction

Lumbar Plexopathy Caused by Metastatic Tumor, Which Was Mistaken for Postoperative Femoral Neuropathy

Surgical excision was performed on a 30-years old woman with a painful mass on her left thigh. The pathologic findings on the mass indicated fibromatosis. After the operation, she complained of allodynia and spontaneous pain at the operation site and ipsilateral lower leg. We treated her based on postoperative femoral neuropathy, but symptom was aggravated. We found a large liposarcoma in her left iliopsoas muscle which compressed the lumbar plexus. In conclusion, the cause of pain was lumbar plexopathy related to a mass in the left iliopsoas muscle. Prompt diagnosis of acute neuropathic pain after an operation is important and management must be based on exact causes

Operative Treatment with a Laparotomy for Anorectal Problems Arising from a Self-Inserted Foreign Body

An anorectal foreign body can cause serious complications such as incontinence, rectal perforation, peritonitis, or pelvic abscess, so it should be managed immediately. We experienced two cases of operative treatment for a self-inserted anorectal foreign body. In one, the foreign body could not be removed as it was completely impacted in the anal canal. We failed to remove it through the anus. A laparotomy and removal of the foreign body was performed by using an incision on the rectum. Primary colsure and a sigmoid loop colostomy were done. A colostomy take-down was done after three months. The other was a rectal perforation from anal masturbation with a plastic device. We performed primary repair of the perforated rectosigmoid colon, and we didea sigmoid loop colostom. A colostomy take-down was done three months later. Immediate and proper treatment for a self-inserted anorectal foreign body is important to prevent severe complications, and we report successful surgical treatments for problems caused by anorectal foreign bodies