Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine

<p>Abstract</p> <p>Background</p> <p>Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat mood and anxiety disorders. However, neuronal bases for both beneficial and adverse effects of SSRIs remain poorly understood. We have recently shown that the SSRI fluoxetine can reverse the state of maturation of hippocampal granule cells in adult mice. The granule cell "dematuration" is induced in a large population of granule cells, and greatly changes functional and physiological properties of these cells. Here we show that this unique form of neuronal plasticity is correlated with a distinct change in behavior of mice.</p> <p>Results</p> <p>We chronically treated adult male mice with fluoxetine, and examined its effect on several forms of behavior of mice. During fluoxetine treatments, mice showed a marked increase in day-to-day fluctuations of home cage activity levels that was characterized by occasional switching between hypoactivity and hyperactivity within a few days. This destabilized cage activity was accompanied by increased anxiety-related behaviors and could be observed up to 4 weeks after withdrawal from fluoxetine. As reported previously, the granule cell dematuration by fluoxetine includes a reduction of synaptic facilitation at the granule cell output, mossy fiber, synapse to the juvenile level. Mossy fiber synaptic facilitation examined electrophysiologically in acute hippocampal slices also remained suppressed after fluoxetine withdrawal and significantly correlated with the fluctuation of cage activity levels in individual mice. Furthermore, in mice lacking the 5-HT₄receptor, in which the granule cell dematuration has been shown to be attenuated, fluoxetine had no significant effect on the fluctuation of cage activity levels.</p> <p>Conclusions</p> <p>Our results demonstrate that the SSRI fluoxetine can induce marked day-to-day changes in activity levels of mice in the familiar environment, and that the dematuration of the hippocampal granule cells is closely associated with the expression of this destabilized behavior. Based on these results, we propose that the granule cell dematuration can be a potential cellular basis underlying switching-like changes in the behavioral state associated with SSRI treatments.</p

Optical Measurement of Cesium Behavior in a Large H− Ion Source for a Neutral Beam Injector

Optical emission in a negative hydrogen ion source for the Large Helical Device Neutral Beam Injector (LHD-NBI) has been measured to investigate the behavior of Cs. Two optical sight lines exist parallel to the plasma grid, in the discharge area and in the magnetic filter area near the plasma grid. In the discharge area, the spectrum intensity from Cs+ ions is considerably increased during 20 s of the beam extraction. This indicates a considerable increase in the Cs+ density inside the plasma due to the impact of back-streaming H+ ions. A strong neutral Cs spectrum is observed in the magnetic filter area, where the electron density is lower than in the discharge area. The rate of increase of neutral Cs is much enhanced after t = 30 s, probably because the Cs adsorbed on the cooled region inside the arc chamber evaporates because its temperature increases during the long pulse discharge

Simultaneous Measurements of Proton Ratio and Beam Divergence of Positive-ion-based Neutral Beam in the Large Helical Device

A spectroscopy system was installed on the diagnostic neutral beam injector in LHD. The Hα lines spectrum emitted by full, half and one-third energy component are clearly observed, and the proton ratio and the beam divergence were estimated by the line intensity and the line width, respectively. The proton ratio of 85?90 % is achieved in high arc power discharge. The beam divergence of them shows their minimum with the same perveance. It was experimentally confirmed that the spectroscopy system is useful for the monitor of the proton ratio and the divergence of the beam

A safe combined nephrectomy and right lobectomy using the liver hanging maneuver for huge renal cell carcinoma directly invading the right lobe of the liver: report of a case

We herein discuss a patient who underwent simultaneous combined right nephrectomy and right lobectomy of the liver. A 64-year-old male was diagnosed with a huge right renal cell carcinoma (RCC), 13 cm in diameter, which was invading directly into the right hepatic lobe. This type of RCC has been rarely reported, and an anterior approach using the liver hanging maneuver was extremely useful during hepatic parenchymal dissection. The liver parenchymal dissection was performed prior to mobilization of the liver, because the mobilization of the right lobe of the liver was impossible. During the hepatic parenchymal resection, the liver was suspended with the tape and transected, and thereafter, retroperitoneal dissection, nephrectomy and right lobectomy of the liver were completed. The patient was discharged from the hospital on the 12th postoperative day with an uneventful clinical course. The anterior approach using the liver hanging maneuver during hepatic parenchymal resection can be safe and feasible for huge RCC invading the right hepatic lobe

Difference of co-extracted electron current and beam acceleration in a negative ion source with hydrogen-isotope ions

Improvement of the performance on a hydrogen/deuterium negative ion source for a nuclear fusion device is reported. In particular, the suppression of the co-extracted electron current, Ie, is an important issue to ensure the stable beam acceleration. Improvement of the Ie has been confirmed by optimizing the magnetic field of the electron deflection magnet in the extraction grid. Two other new methods for reduction of the Ie were validated. The first was an electron fence whose rods were set between the rows of apertures on a plasma grid. The electron and negative ion current ratio, approximately Ie/Iacc, was greatly improved from 0.7 to 0.25 in deuterium. The second was an outer iron yoke which enhanced the magnetic flux density 19% inside the arc discharge chamber. The Ie/Iacc using the outer yoke decreased by 0.1 compared with using a normal magnetic filter in a deuterium operation. These attempts have improved the total deuterium injection beam power of 8.4 MW by three negative ion based NBIs

Visualization of H? Dynamics in Extraction Region of Negative-Ion Source by Hα Imaging Spectroscopy

We developed a new imaging spectroscopy diagnostic tool for Hα emission and installed it on a negative hydrogen ion (H?) source to investigate the H? dynamics in the extraction region. During beam extraction, the Hα emission dropped; the same drop also appeared in the H? density (as measured by cavity ring-down spectroscopy). The reduction in the Hα emission results from the reduction in the excited hydrogen population caused by mutual neutralization processes between H+ and H? ions, which in turn are due to a decrease in the H? density. We find a reduction structure in Hα that is observed inside the plasma farther than 20 mm from the plasma grid (PG) surface. The result indicates that H? ions produced at the PG surface accumulate in the extraction region, so we conclude that they flow toward the PG apertures

LHDにおけるNBI用水素負イオン源とビーム生成の最新の研究成果

The state of hydrogen plasma in the extraction region in a hydrogen negative-ion (H−) source for NBI has been investigated. We clearly observe an improvement of H− density owing to the surface production effect with Cs seeding. H− ions are widely distributed in the extraction region which is obtained by movable cavity ring down (CRD). We confirm a negative ion rich plasma with a few electrons in the extraction region, which state is important for reduction of electron contamination in extracting beam. An extraction area is reached 30mm from the PG surface, which is measured by a 2D imaging diagnostic for Hα emission. We find the insensitive area for H− extraction at the PG surface between the apertures. Negative ions produced at the surface are considered tohave been supplied in the extraction region. The flow velocity of H− ions is obtained by a four-pin Langmuir probe using a photodetachment technique with an Nd:YAG laser. H− ion flows from the plasma grid surface, and its direction drastically changes at 20mm from the production surface. This flow behavior is considered to be an important characteristic for improving H− density in the extraction region

Mechanical Strength of the Mayo Clinic Congruent Elbow Plate System for Distal Humerus Fractures: Cadaveric and Model Bone Model

The purpose of this study was to compare the Mayo Clinic Congruent Elbow Plate System with a plate system having the same biomechanical features as a conventional non-locking system. For testing, we used a biaxial adjustable material testing machine (Mini-Bionix®, MTS, Minnetonka, MN). A compressive load of 500 N/min was applied in the axial direction, and a torque of 30 deg/min was applied in the rotational direction to simulate internal rotation of the elbow. The relationships between force (N) and displacement (mm), and between the internal rotational angle (deg) and torque (N/m), were measured. The Mayo Clinic Congruent Elbow Plate and the two types of screws used in this study may provide sufficient fixation strength. The results obtained here warrant further studies that are more dynamic (e.g., cyclic loading and repetitive torsion tests), with a larger number of specimens, and that facilitate appropriate nomal elbow movement in daily living, to assess the utility of plate fixation with locking and non-locking systems for distal humerus fractures

Exopolysaccharides From Streptococcus thermophilus ST538 Modulate the Antiviral Innate Immune Response in Porcine Intestinal Epitheliocytes

It was reported that exopolysaccharides (EPSs) from lactobacilli are able to differentially modulate mucosal antiviral immunity. Although research has described the ability of EPSs derived from Streptococcus thermophilus to modulate the mucosal immune system, their impact on antiviral immunity was less explored. In this work, we investigated the capacity of the EPS-producing S. thermophilus ST538 to modulate the innate antiviral immune response triggered by the activation of the Toll-like receptor 3 (TLR3) in porcine intestinal epitheliocytes (PIE cells). Moreover, in order to study the immunomodulatory potential of S. thermophilus ST538 EPS, we successfully developed two mutant strains through the knockout of the epsB or epsC genes. High-performance liquid chromatography and scanning electron microscopy studies demonstrated that the wild type (WT) strain produced as high as 595 μg/ml of EPS in the skim milk medium, while none of the mutant strains (S. thermophilus ΔepsB and ΔepsC) were able to produce EPS. Studies in PIE cells demonstrated that the EPS of S. thermophilus ST538 is able to significantly improve the expression of interferon β (IFN-β), interleukin 6 (IL-6), and C-X-C motif chemokine 10 (CXCL10) in response to TLR3 stimulation. The role of EPS in the modulation of antiviral immune response in PIE cells was confirmed by comparative studies of cell free culture supernatants and fermented skim milks obtained from S. thermophilus ΔepsB and ΔepsC. These results suggest that S. thermophilus ST538 could be used as an immunobiotic strain for the development of new immunologically functional foods, which might contribute to improve resistance against viral infections.Fil: Mizuno, Akira. Tohoku University; JapónFil: Tomotsune, Kae. Tohoku University; JapónFil: Islam, Md Aminul. Tohoku University; JapónFil: Funabashi, Ryutaro. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; Japón. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología; ArgentinaFil: Ikeda Ohtsubo, Wakako. Tohoku University; JapónFil: Aso, Hisashi. Tohoku University; JapónFil: Takahashi, Hideki. Tohoku University; JapónFil: Kimura, Katsunori. Meiji Co.; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Sasaki, Yasuko. Meiji University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó

Patched1 Haploinsufficiency Increases Adult Bone Mass and Modulates Gli3 Repressor Activity

SummaryHedgehog (Hh)-Patched1 (Ptch1) signaling plays essential roles in various developmental processes, but little is known about its role in postnatal homeostasis. Here, we demonstrate regulation of postnatal bone homeostasis by Hh-Ptch1 signaling. Ptch1-deficient (Ptch1+/−) mice and patients with nevoid basal cell carcinoma syndrome showed high bone mass in adults. In culture, Ptch1+/− cells showed accelerated osteoblast differentiation, enhanced responsiveness to the runt-related transcription factor 2 (Runx2), and reduced generation of the repressor form of Gli3 (Gli3rep). Gli3rep inhibited DNA binding by Runx2 in vitro, suggesting a mechanism that could contribute to the bone phenotypes seen in the Ptch1 heterozygotes. Moreover, systemic administration of the Hh signaling inhibitor cyclopamine decreased bone mass in adult mice. These data provide evidence that Hh-Ptch1 signaling plays a crucial role in postnatal bone homeostasis and point to Hh-Ptch1 signaling as a potential molecular target for the treatment of osteoporosis