Hiroshi Kaneko

Transient responses of inflammatory cytokines in acute stress

It has been demonstrated that concentrations of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) are elevated by acute stress. Although several studies confirmed robust changes in IL-6, how acute stress affects other cytokines was less clear. Therefore, the present study simultaneously examined the effects of acute stress on several pro-inflammatory cytokines. Sixteen male participants were given the Trier Social Stress Test (TSST). Blood samples were collected at baseline, immediately after, and 30, 60, and 90min after the TSST. IL-1beta significantly increased immediately after the TSST and returned to the baseline level after 30min. Additionally, this elevation of IL-1beta was correlated with the perceived intensity of stress. These results showed that the concentration of IL-1beta is rapidly regulated, and that elevation of the IL-1beta level could possibly be attributed to transient mobilization of monocytes caused by sympathetic nervous activation. Moreover, a transient increase of IL-1beta might be conveyed to the brain and play a role in forming negative emotional states.

Efficacy and safety of oral lubiprostone in constipated patients with or without irritable bowel syndrome: a randomized, placebo‐controlled and dose‐finding study

Backgroundu2002 Lubiprostone is a prostone analog with a novel mechanism of action involving type‐2 chloride channel activation. The aim of this work was to perform a dose‐finding study for lubiprostone for the treatment of constipation with or without irritable bowel syndrome (IBS) in Japan.

Associations among positive mood, brain, and cardiovascular activities in an affectively positive situation.

It is hypothesized that experiencing positive emotions such as pleasure leads to a perception of the body being in a positive state. This study demonstrated associations among positive mood, brain, and cardiovascular activities by simultaneously recording these activities when positive emotions were evoked in participants watching films revolving around a love story. Heart rate variability analysis revealed increased parasympathetic nervous activity while watching the film. The following brain regions were significantly activated in the positive condition relative to the control condition: medial prefrontal cortex, thalamus, superior temporal gyrus, inferior frontal gyrus, and cerebellum. Further, covariate analyses indicated that these brain regions were temporally associated with subjective positive mood. Activities of brain regions considered to be related to interoceptive awareness, such as the insular cortex, anterior cingulate cortex, amygdala, and orbitofrontal cortex, were also temporally associated with the cardiovascular change. These results suggest that while an individual experiences positive emotions, activities of the central nervous system and cardiovascular system may be interrelated, and the brain may perceive the body to be in a positive state.

Inhibitory effect of oxytocin on accelerated colonic motility induced by water-avoidance stress in rats

Abstractu2002 Recent studies have indicated that brain and gut activities are interrelated and exposure to several stressors, such as water‐avoidance stress, stimulates the motor function of the gut through corticotropin‐releasing factor (CRF)‐signalling pathways in the brain. Central oxytocin is known to attenuate stress responses, including CRF expression in the brain. Here, we examined whether central oxytocin attenuated the acceleration of colonic motility induced by water‐avoidance stress. A force transducer was attached to the distal colon of male rat, and the colonic motility and faecal pellet output were recorded while the rats were exposed to water‐avoidance stress. Intracerebroventricular (i.c.v.) injections of oxytocin (5, 50 and 500u2003pmol) and the oxytocin receptor antagonist tocinoic acid (25u2003μg) were administered before exposure to water‐avoidance stress, and the effect of oxytocin on colonic motor function was determined. Centrally administered oxytocin inhibited the accelerated colonic motility induced by water‐avoidance stress. The effective dose ranged between 5 and 50u2003pmol on i.c.v. injection. Oxytocin also decreased the number of CRF‐positive cells in the paraventricular nucleus and corticosterone release. The inhibitory effect of oxytocin on accelerated colonic motility was blocked by pretreatment with oxytocin receptor antagonist. Furthermore, centrally administered tocinoic acid enhanced the acceleration of colonic motility. These results suggested that endogenous central oxytocin may contribute to the regulation of colonic function and inhibit the brain CRF‐signalling pathways targeting the gut, resulting in the inhibition of stress‐induced colonic contractions.

Association of polymorphism in the human μ-opioid receptor OPRM1 gene with proinflammatory cytokine levels and health perception

Recent studies in psychoneuroimmunology have indicated that proinflammatory cytokines cause several diseases and behaviors that overlap symptomatically with depression. It is known that the endogenous opioid peptide beta-endorphin regulates proinflammatory cytokine secretion from peripheral immune cells via mu-opioid receptor-dependent mechanisms. Therefore, it is possible that the functional polymorphism of the mu-opioid receptor gene (OPRM1, SNP: A118G) influences peripheral circulating proinflammatory cytokine levels and the health-related quality of life (QOL) even in healthy populations. In this study, we compared the serum concentrations of several proinflammatory cytokines (interleukin-2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma)) and the health-related QOL between OPRM1 genotypes. Interestingly, serum concentrations of IL-6, TNF-alpha, and IFN-gamma were significantly lower and the general health score was significantly higher in carriers of the G allele, who show a strong binding of beta-endorphin to the mu-opioid receptor as compared to individuals without the G allele. Correlation analysis indicated that the general health score was negatively correlated with the IL-6 serum concentration. These results suggest that the sensitive endogenous opioid system in carriers of the G allele may suppress proinflammatory cytokine secretion from peripheral immune cells; consequently, it may influence the health perception.

Genetic variations in the serotonin transporter gene-linked polymorphic region influence attraction for a favorite person and the associated interactions between the central nervous and immune systems.

Limbic system activation that occurs when a person experiences several emotions is primarily represented by the amygdala output that influences autonomic brainstem nuclei that control autonomic nervous function, thus modulating the endocrine and immune systems. Amygdala activity is modulated by the serotonin transporter gene-linked polymorphic region (5HTTLPR); however, whether variations in 5HTTLPR influence central nervous and immune activities in response to positive stimuli remains unclear. Here, we found that seeing a favorite person induced significantly higher amygdala activity in individuals with the 5HTTLPR SS genotype than in others. This activity was positively correlated with changes in the NK cell proportion among peripheral lymphocytes. Thus, 5HTTLPR influences attraction and the associated interactions between the central nervous and immune systems in affectively positive situations.

99. The serum levels of n-3 fatty acids and IL-6 were independently associated with depressive symptoms in female population

Inflammation, oxidation and some fatty acids (FAs) have been addressed in relation to depression. To investigate these associations, we compared perceived depression with peripheral serum FAs, inflammatory and oxidative stress markers. We conducted a cross-sectional study on 141 female workers in a hospital and nursing homes. Depressive symptoms were assessed utilizing the 20-item Center for Epidemiologic Studies Depression (CES-D) scale. FAs, IL-6 cytokine, hs-CRP and oxidised (ox-) LDL in the serum from the peripheral blood were measured. Prior to data analysis, two participants taking sleeping drug, and nine whose serum triglyceride levels were over 200xa0mg/dl were excluded; consequently, 129 subjects were analysed. After controlling for confounders, CES-D scores were negatively correlated with the serum concentration and percentage of n-3 poly-unsaturated FAs (PUFAs: Docosahexaenoic acid, DHA; Eicosapentaenoic acid, EPA), and positively correlated with IL-6 concentrations, whereas there were no significant correlations between CES-D scores and either hs-CRP or ox-LDL concentrations. Hierarchical linear regression analysis revealed that IL-6 and n-3 PUFA were independently related with CES-D scores (p

Depressive symptoms of female nursing staff working in stressful environments and their association with serum creatine kinase and lactate dehydrogenase – a preliminary study

BackgroundThe activity of creatine kinase (CK) in serum has recently been reported to be potentially associated with several types of depression. The aim of this study is to evaluate whether serum enzymes, including CK, vary even in a healthy population with depressive symptoms caused by work-related stress. We gave questionnaires and blood examinations to 93 healthy female nursing home workers and did an enzyme-linked immunosorbent assay for the quantitative detection of CK isozyme muscle-type M chain (CK-MM) in serum.FindingsDepressive symptoms were determined using the Center for Epidemiologic Studies Depression (CES-D) scale and compared with the results of the blood examination and serum CK-MM levels. The CES-D results showed significant negative correlations with total CK and lactate dehydrogenase (LDH) activities and CK-MM level (ru2009=u2009-0.29, pu2009=u20090.0062; ru2009=u2009-0.29, pu2009=u20090.0065; ru2009=u2009-0.33, pu2009=u20090.0016, respectively).ConclusionsTotal CK and LDH activities and serum CK-MM level appear to be associated with the depressive symptoms of healthy nurses working in stressful environments, although the significance level was relatively low. The simultaneous detection of serum CK and LDH activities or serum CK-MM level and LDH activity may be useful as an indicator of depressive symptoms, at least for female nursing staff with work-related stress.

Analysis on Awareness of Functional Dyspepsia and Rome Criteria Among Japanese Internists by the Self-administered Questionnaires.

Background/Aims Functional dyspepsia (FD) is one of the commonest diseases in the field of Internal Medicine. The Japanese Society of Gastroenterology (JSGE) has been enlightening the term and concept of FD. Aim of this survey was to elucidate the understanding status of FD and Rome criteria and attitude toward FD among Japanese internists. Methods Data were collected at the time of lifelong education course for certified members of Japanese Society of Internal Medicine. Self-administered questionnaires were delivered to the medical doctors prior to the lectures. Results Analysis subjects were 1,623 (24-90 years old) internists among 1,660 medical doctors out of 4,264 attendees. The terms related to FD were known in 62.0-68.9% of internists, whereas 95.5% understood chronic gastritis. Internists who had been taking care of FD patients informed them as chronic gastritis (50.0%), FD in Japanese Kanji character (50.8%) and FD in Kanji and Katakana (18.6%). Logistic linear regression analysis revealed that positive factors for the understanding of FD and intensive care for FD patients were practitioner, caring many patients and certified physician by JSGE. Existence of Rome criteria was known in 39.9% of internists, and 31.8% out of them put it to practical use. The certified physician by JSGE was a positive factor for awareness, but not for utilization. Conclusions The results suggest the needs of enlightening the medical term FD in Japan and revision of Rome criteria for routine clinical practice. Precise recognition of FD may enhance efficient patient-based clinical practice.

Profiling of serum proteins associated with subjective happiness

s S187 prefrontal, orbitofrontal and temporal cortices. But there was no region in which BP in males was higher than that in females. These results were in accordance with the precedent animal studies. The significant gender difference in H1 receptors may be related to the cognitive difference between male and female. PET is a promising method to study the underlined mechanism for brain diseases which are frequent in women such as anorexia nervosa. doi:10.1016/j.neures.2009.09.1003 P2-m09 Profiling of serum proteins associated with subjective happiness Masahiro Matsunaga1,2, Tokiko Isowa3, Hirohito Tsuboi1, Yoko Kawanishi1, Masashi Yoneda2, Kunio Kasugai2, Hideki Ohira4, Hiroshi Kaneko1 1 Fujita Health University, Japan; 2 Aichi Medical University, Japan; 3 Mie University, Japan; 4 Nagoya University, Japan Recent studies in psychoneuroimmunology have suggested that positive emotions, such as happiness, may positively influence our health; however, it has not been investigated yet whether serum proteins are influenced by subjective happiness. In this study, we compared the serum concentrations of several proinflammatory cytokines, which cause sickness behaviors that overlap symptomatically with depression, between high and low happiness groups. Furthermore, serum protein profile was compared by using ProteinChip surface enhanced laser desorption/ionization-time-of-flight-mass spectrometry (SELDI-TOF-MS). Serum concentrations of proinflammatory cytokines were significantly lower in higher happiness group. SELDI-TOF-MS indicated that the intensities of 3.3-k Da, 6.6-k Da, and 9.1-kDa serum proteins were higher in higher happiness group. These results suggest that subjective happiness may influence serum levels of proinflammatory cytokines and several serum proteins associated with health. doi:10.1016/j.neures.2009.09.1004 P2-m10 Effect of corticosterone on dendritic spines in rat hippocampus Yoshimasa Komatsuzaki1,2,3, Masatoshi Kasuya2,3, Yasushi Hojo2,3, Suguru Kawato2,3 1 Dept of Physics, CST, Nihon Univ, Japan; 2 Grad Sch of Arts and Sci, Univ of Tokyo, Japan; 3 Bioinformatics Project, JST, Japan Modulation of hippocampal synaptic plasticity by corticosterone (CORT) has been attracting much attention, due to its importance in stress responses. Dendritic spines are essential for memory storage processes. We investigated effect of CORT, a major glucocorticoid in rat, on density and morphology of dendritic spines in adult male rat hippocampus by imaging of Lucifer Yellow-injected spines in slices. The application of 1 M CORT induced the rapid increase of the density and morphology of dendritic spines in CA1 pyramidal neurons within 1 h. This CORT effect was mediated by classical glucocorticoid receptor (GR) on dendritic spine. Because the presence of actinomycin D, an inhibitor of gene transcription, did not suppress the CORT effect, this response is probably non-genomic and not mediated via slow genetic processes. Antagonism of NMDA receptors during exposure to CORT prevented the increase of the spine density. Furthermore, the CORT effect on dendritic spine may be involved in activation of Erk MAPK signaling pathway. doi:10.1016/j.neures.2009.09.1005 P2-m11 Post translational modification under ER stress Ryusuke Kuwahara1, Shinsuke Matsuzaki1, Tsuyoshi Hattori1, Yasutake Mori1, Keisuke Kawamoto1, Shoko Shimizu1, Kohei Yamada1, Taiichi Katayama2, Masaya Tohyama1 1 Department of Anatomy and Neuroscience, Osaka University Graduate School of Medicine, Osaka; 2 United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of Medicine Department of Child Development, Japan ER stress response can control translational regulation.We examine the mechanism of translationala control from the aspect of post translational modification. doi:10.1016/j.neures.2009.09.1006 P2-m12 Effects of green odor on serotonin and dopamine metabolites in lateral hypothalamus of rats with emotional stress Kazuo Sasaki1, Naoyuki Yoshimura1, Kazuki Nakajima1, Yutaka Oomura2 1 Div. of Bio-Inf. Eng., Fac. of Eng., University of Toyama, Japan; 2 Integrative Physiol., Kyushu University, Fukuoka, Japan We examined the effects of green odor (GO) on alterations of brain serotonin (5-HT) and dopamine (DA) metabolites in rats with emotional stress (ES). ES is given to rats by exposing them into an environment in which they can observe the behavior of other rats who receive electrical foot shock. GO was also given to rats with ES by inhalation. For measurements of 5-HT and DA metabolites, perfusates were obtained from the lateral hypothalamus by microdialysis method, and analyzed by HPLC. Levels of a 5-HT metabolite (5-HIAA) and DA metabolites (DOPAC and HVA) in control rats increased gradually after the beginning of ES, and 75 min later reached to a plateau level about 1.2 times greater than basal level. In rats with GO, the alterations of the 5-HIAA levels were almost similar to those in controls. However, the increases of the DOPAC and HVA levels were significantly smaller in rats with GO than in control rats. Results suggest that GO may inhibit dopaminergic activity activated by ES. doi:10.1016/j.neures.2009.09.1007 P2-m13 Genetic analyses of mechanisms for memory loss in Caenorhabditis elegans Akitoshi Inoue, Takeshi Ishihara Kyushu University, Japan An acquired short-term memory is usually forgotten within hours, although it is sometimes transformed into a stable long-term memory. However, the mechanisms of the memory loss processes remain largely unknown. Since C. elegans possesses a simple nervous system and their memories usually do not persist more than hours, it is suitable to study the mechanisms of memory loss of the short term memory at the molecular level. To elucidate the processes, we screened and isolated mutants defective in memory loss, by using two types of behavioral plasticity as models for learning, the olfactory adaptation and the salt chemotaxis learning. These mutants show prolonged retention of memory for these behavioral plasticities. We mapped the mutation of these mutants in the center of chromosome III, where tir-1 which encodes an ortholog of SARM, a Toll interleukin 1 receptor (TIR) domain protein is located. We found that tir-1 mutants show prolonged retention of memory for olfactory adaptation. The analyses of the gene will reveal molecular mechanisms of the memory loss processes. doi:10.1016/j.neures.2009.09.1008 P2-m14 Pharmacological discrimination of fear extinction and reconsolidation Daisuke Yamada1,2, Keiji Wada1,2, Masayuki Sekiguchi1,2 1 Dept Degenet Neurol Dis, Natl Inst Neurosci, NCNP, Japan; 2 JST, CREST,