Anesthesia and Post-mortem Interval Profoundly Influence the Regulatory Serine Phosphorylation of Glycogen Synthase Kinase-3 in Mouse Brain

Glycogen synthase kinase-3 (GSK3) is a crucial enzyme contributing to the regulation of neuronal structure, plasticity and survival, is implicated as a contributory factor in prevalent diseases such as Alzheimer’s disease and mood disorders and is regulated by a wide range of signaling systems and pharmacological agents. Therefore, factors regulating GSK3 in vivo are currently of much interest. GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3β and GSK3α, respectively. This study found that accurate measurements of phospho-Ser-GSK3 in brain are confounded by a rapid post-mortem dephosphorylation, with ~90% dephosphorylation of both GSK3 isoforms occurring within 2 min post-mortem. Furthermore, three anesthetics, pentobarbital, halothane and chloral hydrate, each caused large in vivo increases in the serine phosphorylation of both GSK3β and GSK3α in several regions of mouse brain. Thus, studies of the phosphorylation state of GSK3 in brain, and perhaps in other tissues, need to take into account post-mortem changes and the effects of anesthetics and there is a direct correlation between anesthesia and high levels of serine-phosphorylated GSK3

The effects of repeated administrations of MK-801 on ERK and GSK-3beta signalling pathways in the rat frontal cortex

Repeated administrations of NMDA receptor antagonists induce behavioural changes which resemble the symptoms of schizophrenia in animals. ERK and GSK-3beta associated signalling pathways have been implicated in the pathogenesis of psychosis and in the action mechanisms of various psychotropic agents. Here, we observed the phosphorylations of ERK and GSK-3beta and related molecules in the rat frontal cortex after repeated intraperitoneal injections of MK-801, over periods of 1, 5, and 10 d. Repeated treatment with 0.5, 1, and 2 mg/kg MK-801 increased the phosphorylation levels of the MEK-ERK-p90RSK and Akt-GSK-3beta pathways and concomitantly and significantly increased CREB phosphorylation in the rat frontal cortex. However, single MK-801 treatment did not induce these significant changes. In addition, the immunoreactivities of HSP72, Bax, and PARP were not altered, which suggests that neuronal damage may not occur in the rat frontal cortex in response to chronic MK-801 treatment. These findings suggest that chronic exposure to MK-801 may induce pro-survival and anti-apoptotic activity without significant neuronal damage in the rat frontal cortex. Moreover, this adaptive change might be associated with the psychotomimetic action of MK-801

Measuring stress in medical education: validation of the Korean version of the higher education stress inventory with medical students

Background: Medical students face a variety of stressors associated with their education; if not promptly identified and adequately dealt with, it may bring about several negative consequences in terms of mental health and academic performance. This study examined psychometric properties of the Korean version of the Higher Education Stress Inventory (K-HESI). Methods: The reliability and validity of the K-HESI were examined in a large scale multi-site survey involving 7110 medical students. The K-HESI, Beck Depression Inventory (BDI) and questions regarding quality of life (QOL) and self-rated physical health (SPH) were administered. Results: Exploratory factor analysis of the K-HESI identified seven factors: Low commitment; financial concerns; teacher-student relationship; worries about future profession; non-supportive climate; workload; and dissatisfaction with education. A subsequent confirmatory factor analysis supported the 7-factor model. Internal consistency of the K-HESI was satisfactory (Cronbach's a = .78). Convergent validity was demonstrated by its positive association with the BDI. Known group validity was supported by the K-HESI's ability to detect significant differences on the overall and subscale scores of K-HESI according to different levels of QOL and SPH. Conclusions: The K-HESI is a psychometrically valid tool that comprehensively assesses various relevant stressors related to medical education. Evidence-based stress management in medical education empirically guided by the regular assessment of stress using reliable and valid measure is warranted.open

AKT1 Gene Polymorphisms and Obstetric Complications in the Patients with Schizophrenia

ObjectiveaaWe performed a genetic association study with schizophrenic patients to investigate whether the V-akt murine thymoma viral oncogene homolog 1 (AKT1) gene plays a role in obstetric complications. MethodsaaOne-hundred-eighty patients with schizophrenia (male, 113; female, 67) were included. All patients fulfilled DSM-IV criteria for schizophrenia. Obstetric complications were measured by the Lewis scale. Prenatal and perinatal information was retrospectively collected from the patients ’ mothers. We selected six single nucleotide polymorphisms (SNPs) for the AKT1 gene: SNP1 (rs3803300), SNP2 (rs1130214), SNP3 (rs3730358), SNP4 (rs 1130233), SNP5 (rs2494732), and SNPA (rs2498804). The genotype data were analyzed for an association with the Lewis total score in terms of allele, genotype, and haplotype distribution. ResultsaaThe mean total Lewis scores were 1.30±1.61 for males and 1.54±1.87 for females. Higher total score tended to be correlated with an earlier age of onset of schizophrenia in females. In the total sample, no SNP was associated with obstetric complications. However, the additional analyses for male and female subgroups found a significant associatio

The First Very Long Baseline Interferometry Image of 44 GHz Methanol Maser with the KVN and VERA Array (KaVA)

We have carried out the first very long baseline interferometry (VLBI) imaging of 44 GHz class I methanol maser (7_{0}-6_{1}A^{+}) associated with a millimeter core MM2 in a massive star-forming region IRAS 18151-1208 with KaVA (KVN and VERA Array), which is a newly combined array of KVN (Korean VLBI Network) and VERA (VLBI Exploration of Radio Astrometry). We have succeeded in imaging compact maser features with a synthesized beam size of 2.7 milliarcseconds x 1.5 milliarcseconds (mas). These features are detected at a limited number of baselines within the length of shorter than approximately 650 km corresponding to 100 Mlambda in the uv-coverage. The central velocity and the velocity width of the 44 GHz methanol maser are consistent with those of the quiescent gas rather than the outflow traced by the SiO thermal line. The minimum component size among the maser features is ~ 5 mas x 2 mas, which corresponds to the linear size of ~ 15 AU x 6 AU assuming a distance of 3 kpc. The brightness temperatures of these features range from ~ 3.5 x 10^{8} to 1.0 x 10^{10} K, which are higher than estimated lower limit from a previous Very Large Array observation with the highest spatial resolution of ~ 50 mas. The 44 GHz class I methanol maser in IRAS 18151-1208 is found to be associated with the MM2 core, which is thought to be less evolved than another millimeter core MM1 associated with the 6.7 GHz class II methanol maser.Comment: 19 pages, 3 figure

No Association of Functional Polymorphisms in Methlylenetetrahydrofolate Reductase and the Risk and Minor Physical Anomalies of Schizophrenia in Korean Population

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia

Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions

Glycogen synthase kinase-3 (GSK3) has recently been linked to mood disorders and schizophrenia, and the neurotransmitter systems and therapeutic treatments associated with these diseases. GSK3 is a widely influential enzyme that is capable of phosphorylating, and thereby regulating, over forty known substrates. Four mechanisms regulating GSK3 (phosphorylation, protein complexes, localization, and substrate phosphorylation) combine to provide substrate-specific regulation of the actions of GSK3. Several intracellular signaling cascades converge on GSK3 to modulate its activity, and several neurotransmitter systems also regulate GSK3, including serotonergic, dopaminergic, cholinergic, and glutamatergic systems. Because of changes in these neurotransmitter systems and the actions of therapeutic drugs, GSK3 has been linked to the mood disorders, bipolar disorder and depression, and to schizophrenia. Inhibition of GSK3 may be an important therapeutic target of mood stabilizers, and regulation of GSK3 may be involved in the therapeutic effects of other drugs used in psychiatry. Dysregulated GSK3 in bipolar disorder, depression, and schizophrenia could have multiple effects that could impair neural plasticity, such as modulation of neuronal architecture, neurogenesis, gene expression, and the ability of neurons to respond to stressful, potentially lethal, conditions. In part because of these key actions of GSK3 and its associations with mood disorders and schizophrenia, much research is currently being devoted to identifying new selective inhibitors of GSK3

Up-regulation of cocaine- and amphetamine-regulated transcript (CART) in the rat nucleus accumbens after repeated electroconvulsive shock

Cocaine- and amphetamine-regulated transcript (CART) peptide regulates appetite, reward, and mood. CART expression is regulated via the protein kinase A (PKA) pathway, and electroconvulsive shock (ECS), an efficient antipsychotic and antidepressant measure, activates PKA-related signaling. Thus, we hypothesized that ECS may regulate the expression of CART. ECS given daily for five consecutive days increased CART mRNA and protein in the rat nucleus accumbens (NAc), accompanied by an increase in CREB phosphorylation. Our results suggest that ECS-induced CART up-regulation might be associated with PKA-CREB signaling, but the causal direction remains to be elucidated in future studies. (C) 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.This study was supported by a grant (KRF-2005-04-E00233) from the Korean Research Foundation and a research fund by Shin Hae Choi (2002) from the Korean Neuropsychiatric Association.Jaworski JN, 2008, BEHAV BRAIN RES, V191, P266, DOI 10.1016/j.bbr.2008.03.039Jones DC, 2008, SYNAPSE, V62, P122Hubert GW, 2008, BIOCHEM PHARMACOL, V75, P57, DOI 10.1016/j.bcp.2007.07.028Yoon HS, 2007, NEUROPHARMACOLOGY, V53, P344, DOI 10.1016/j.neuropharm.2007.05.014Ma ZY, 2007, NEUROSCI LETT, V417, P303, DOI 10.1016/j.neulet.2007.02.049Pae CU, 2007, MED HYPOTHESES, V69, P132, DOI 10.1016/j.mehy.2006.11.009Dominguez G, 2006, PEPTIDES, V27, P1913, DOI 10.1016/j.peptides.2006.01.025del Giudice EM, 2006, DEPRESS ANXIETY, V23, P90, DOI 10.1002/da.20156Yang SC, 2004, EUR J PHARMACOL, V494, P179, DOI 10.1016/j.ejphar.2004.05.018Jaworski JN, 2003, LIFE SCI, V73, P741, DOI 10.1016/S0024-3205(03)00394-1Carlezon WA, 1998, SCIENCE, V282, P2272Koylu EO, 1998, J COMP NEUROL, V391, P115PAXINOS G, 1998, RAT BRAIN STEROTAXICJeon SH, 1997, NEUROPHARMACOLOGY, V36, P411DOUGLASS J, 1995, J NEUROSCI, V15, P2471

Evaluation of Empathy Among Korean Medical Students: A Cross-Sectional Study Using the Korean Version of the Jefferson Scale of Physician Empathy

Background: Empathy is an essential element of physician professionalism. Thus, proper evaluation and education of empathy in medical students is important for medical education. Purpose: This study was conducted to evaluate the psychometric properties of the Korean Student-Version of the Jefferson Scale of Physician Empathy (JSPE-S). Methods: The scale was completed cross-sectionally by 493 medical students at Seoul National University College of Medicine in Korea. Results: Item-total correlations were all positive and statistically significant. Cronbach`s coefficient alpha was 0.84. A factor structure similar to that from American medical students was observed. The mean score of 5.2 +/- 0.6 was obtained. Significant differences in the empathy scores were observed among years in medical school but not between genders. Conclusions: Our findings provide support for the reliability and validity of the Korean JSPE-S and indicate that it can serve as a useful instrument for assessing empathy among Korean medical students.This study was supported by a grant from the Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Republic of Korea.Morling B, 2008, PERS SOC PSYCHOL REV, V12, P199, DOI 10.1177/1088868308318260Neumann M, 2007, PATIENT EDUC COUNS, V69, P63, DOI 10.1016/j.pec.2007.07.003Lown BA, 2007, J GEN INTERN MED, V22, P1514, DOI 10.1007/s11606-007-0318-xChen D, 2007, J GEN INTERN MED, V22, P1434, DOI 10.1007/s11606-007-0298-xSatterfield JM, 2007, MED EDUC, V41, P935, DOI 10.1111/j.1365-2923.2007.02835.xGlaser KM, 2007, MED SCI MONITOR, V13, pCR291Thomas MR, 2007, J GEN INTERN MED, V22, P177, DOI 10.1007/s11606-006-0039-6HOJAT M, 2007, EMPATHY PATIENT CAREWEST CP, 2007, BMC MED EDUC, V7, P29Stepien KA, 2006, J GEN INTERN MED, V21, P524, DOI 10.1111/j.1525-1497.2006.00443.xKLISZCZ J, 2006, ADV MED SCI, V51, P219Alcorta-Garza A, 2005, SALUD MENT, V28, P57Hojat M, 2004, MED EDUC, V38, P934, DOI 10.1111/j.1365-2929.2004.01911.xSpencer J, 2004, MED EDUC, V38, P916, DOI 10.1111/j.1365-2929.2004.01965.xHojat M, 2002, ACAD MED, V77, pS58Hojat M, 2002, AM J PSYCHIAT, V159, P1563Hojat M, 2002, MED EDUC, V36, P522Winefield HR, 2000, MED EDUC, V34, P90DISEKER RA, 1981, J MED EDUC, V56, P1004