416 research outputs found
Stress, Microglial Activation, and Mental Disorders
Microglia play a major role in immune response in the brain. Recent progress in studies for microglia suggests that stress causes morphological alterations in microglia and affects microglial humoral release and phagocytosis. In this review, we present a molecular mechanism by which stress impacts microglia. Then, we describe current findings for the involvement of microglia in stress-related mental disorders including posttraumatic stress disorder (PTSD), depression, and pain enhancement. We focus on preclinical and clinical studies. Preclinical PTSD studies using animal models with fear memory dysregulation show neuroinflammation by microglia and altered microglial phagocytosis, two imaging studies and a postmortem study assessing neuroinflammation in PTSD patients show contradictory results. Imaging studies suggest neuroinflammation in depressed patients, postmortem studies show no microglial inflammatory changes in non-suicidal depressed patients. Although it has been established that microglia in the spinal cord play a pivotal role in chronic neuropathic pain, several preclinical studies suggest microglia also participate in stress-induced pain. A clinical study with induced microglia-like (iMG) cells and an imaging study indicate neuroinflammation by microglia in fibromyalgia patients. We believe that progress in interactive research between humans and animals elucidates the role of microglia in the pathophysiology of stress-related mental disorders
Clarifying the Pathophysiological Mechanisms of Neuronal Abnormalities of NF1 by Induced-Neuronal (iN) Cells from Human Fibroblasts
Direct conversion techniques, which generate induced-neuronal (iN) cells from human fibroblasts in less than two weeks, are expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene expression and cell morphology profiles in iN cells derived from neurofibromatosis type 1 (NF1) patients. NF1 is a single-gene multifaceted disorder with relatively high co-occurrence of autism spectrum disorder (ASD). Adenylyl cyclase (AC) dysfunction is one of the candidate pathways in abnormal neuronal development in the brains of NF1 patients. In our study, microarray-based transcriptomic analysis of iN cells from healthy controls (males) and NF1 patients (males) revealed significantly different gene expression of 149 (110 were upregulated and 39 were downregulated). In iN cells derived from NF1 patients (NF1-iN cells), there was a change in the expression level of 90 genes with the addition of forskolin, an AC activator. Furthermore, treatment with forskolin dramatically changed the cell morphology, especially that of NF1-iN cells, from flat-form to spherical-form. Current pilot data indicate the potential therapeutic effect of forskolin or AC activators on neuronal growth in NF1 patients. Further translational research is needed to validate the pilot findings for future drug development of ASD
The RNA-binding protein Msi2 regulates autophagy during myogenic differentiation
Skeletal muscle development is a highly ordered process orchestrated transcriptionally by the myogenic regulatory factors. However, the downstream molecular mechanisms of myogenic regulatory factor functions in myogenesis are not fully understood. Here, we identified the RNA-binding protein Musashi2 (Msi2) as a myogenin target gene and a post-transcriptional regulator of myoblast differentiation. Msi2 knockdown in murine myoblasts blocked differentiation without affecting the expression of MyoD or myogenin. Msi2 overexpression was also sufficient to promote myoblast differentiation and myocyte fusion. Msi2 loss attenuated autophagosome formation via down-regulation of the autophagic protein MAPL1LC3/ATG8 (LC3) at the early phase of myoblast differentiation. Moreover, forced activation of autophagy effectively suppressed the differentiation defects incurred by Msi2 loss. Consistent with its functions in myoblasts in vitro, mice deficient for Msi2 exhibited smaller limb skeletal muscles, poorer exercise performance, and muscle fiber-type switching in vivo. Collectively, our study demonstrates that Msi2 is a novel regulator of mammalian myogenesis and establishes a new functional link between muscular development and autophagy regulation
Alternating spin chains with singlet ground states
We investigate low-energy properties of the alternating spin chain model
composed of spin and with a singlet ground state. After examining
the spin-wave spectrum in detail, we map low-energy spin excitations to the
O(3) non-linear sigma model in order to take into account quantum fluctuations.
Analyzing the topological term in the resulting sigma model, we discuss how the
massless or massive excitations are developed, especially according to the
topological nature of the alternating spin system.Comment: 9 pages, revtex, to appear in PR
Development and validation of the 25â item Hikikomori Questionnaire (HQâ 25)
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146508/1/pcn12691_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146508/2/pcn12691.pd
Alternating-Spin Ladders
We investigate a two-leg spin ladder system composed of alternating-spin
chains with two-different kind of spins. The fixed point properties are
discussed by using spin-wave analysis and non-linear sigma model techniques.
The model contains various massive phases, reflecting the interplay between the
bond-alternation and the spin-alternation.Comment: 6 pages, revtex, to appear in PR
Suicidal ideation and burnout among psychiatric trainees in Japan
AIM: Burnout is a psychological condition that may occur in all workers after being exposed to excessive work-related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International. METHODS: In the Japanese branch, 91 trainees fully completed suicide ideation and behaviour questionnaire (SIBQ) and Maslach Burnout Inventory-General Survey (MBI-GS). RESULTS: Passive suicidal ideation was reported by 38.5% of Japanese trainees and 22.0% of them had experienced active suicidal ideation. The burnout rate among Japanese subjects was 40.0%. These results were worse compared to the all 1980 trainees who fully completed the main outcome measure in BoSS International, 25.9%, 20.4% and 36.7%, respectively. CONCLUSIONS: Our results suggest a higher risk of suicide among Japanese residents. Japan has a higher suicide rate than other countries. Early detection of, and appropriate intervention for, suicidal ideation is important in preventing suicide in psychiatry residents
Near Infrared Imaging Survey of Bok Globules: Density Structure
On the basis of near-infrared imaging observations, we derived visual
extinction (Av) distribution toward ten Bok globules through measurements of
both the color excess (E_{H-K}) and the stellar density at J, H, and Ks (star
count). Radial column density profiles for each globule were analyzed with the
Bonnor-Ebert sphere model. Using the data of our ten globules and four globules
in the literature, we investigated the stability of globules on the basis of
xi_max, which characterizes the Bonnor-Ebert sphere as well as the stability of
the equilibrium state against the gravitational collapse. We found that more
than half of starless globules are located near the critical state (xi_max =
6.5 +/- 2). Thus, we suggest that a nearly critical Bonnor-Ebert sphere
characterizes the typical density structure of starless globules. Remaining
starless globules show clearly unstable states (xi_max > 10). Since unstable
equilibrium states are not long maintained, we expect that these globules are
on the way to gravitational collapse or that they are stabilized by non-thermal
support. It was also found that all the star-forming globules show unstable
solutions of xi_max >10, which is consistent with the fact that they have
started gravitational collapse. We investigated the evolution of a collapsing
gas sphere whose initial condition is a nearly critical Bonnor-Ebert sphere. We
found that the column density profiles of the collapsing sphere mimic those of
the static Bonnor-Ebert spheres in unstable equilibrium. The collapsing gas
sphere resembles marginally unstable Bonnor-Ebert spheres for a long time. We
found that the frequency distribution of xi_max for the observed starless
globules is consistent with that from model calculations of the collapsing
sphere.Comment: Accepted for publication in the Astronomical Journal. 39 pages in
preprint format, including 10 figures. The version with higher resolution
figures can be obtained at the following site
(http://alma.mtk.nao.ac.jp/~kandori/preprint/
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