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Search Results: 1 - 10 of 1676 matches for " Tetsuya Mizuno "
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The Biphasic Role of Microglia in Alzheimer's Disease
Tetsuya Mizuno
International Journal of Alzheimer's Disease , 2012, DOI: 10.1155/2012/737846
Abstract: Neuroinflammation is involved in the pathogenesis of Alzheimer's disease (AD). Microglia, macrophage-like resident immune cells in the brain, play critical roles in the inflammatory aspects of AD. Microglia may be activated by oligomeric and fibrillar species of amyloid β (Aβ) that are constituents of senile plaques and by molecules derived from degenerated neurons, such as purines and chemokines, which enhance their migration and phagocytosis. The main neurotoxic molecules produced by activated microglia may be reactive oxygen species, glutamate, and inflammatory cytokines such as tumor-necrosis-factor-α and interleukin- (IL-) 1β These molecules differentially induce neurotoxicity. Aβ itself directly damages neurons. In terms of neuroprotective properties, microglia treated with fractalkine or IL-34 attenuate Aβ neurotoxicity by Aβ clearance and the production of antioxidants. Therefore, regulation of the microglial role in neuroprotection may be a useful therapeutic strategy for AD. 1. Introduction Microglia, macrophage-like immune cells in the central nervous system (CNS), cluster around the senile plaques that along with polymorphous amyloid β (Aβ) deposits are the pathological hallmarks of Alzheimer’s disease (AD). Microglia have a biphasic neurotoxic-neuroprotective role in the pathogenesis of AD. In regard to their neurotoxic properties, microglia may be involved in the inflammatory component of AD [1, 2]. In AD, the trigger molecule for microglial activation may be Aβ and molecules derived from degenerated neurons may enhance microglial neurotoxicity [3]. Aβ exists in different assembly forms including monomers, oligomers, and fibrils. Both oligomeric Aβ (oAβ) and fibrillar Aβ (fAβ) have been shown to stimulate microglial secretion of proinflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor-necrosis-factor-α (TNF-α); chemokines including monocyte chemotactic-1 (MCP-1) and macrophage inflammatory protein-1 (MIP-1); complement components; free radicals such as reactive oxygen species (ROS), including superoxide anions and hydroxy radicals [4, 5]. Glutamate also plays an important role in microglial neurotoxicity in AD. Activated microglia produce large amounts of glutamate, which induces excitotoxicity via N-methyl-D-aspartate (NMDA) receptor signaling [6–9]. Chronic activation of extrasynaptic NMDA receptors leads to increased Aβ production [10]. Aβ itself is toxic to neurons in AD, with oAβ being more toxic than fAβ (Figure 1). The toxicity of oAβ manifests itself in terms of synaptic dysfunction, including inhibition of
Static black hole uniqueness and Penrose inequality
Ryosuke Mizuno,Seiju Ohashi,Tetsuya Shiromizu
Physics , 2009, DOI: 10.1103/PhysRevD.81.044030
Abstract: Under certain conditions, we give a new way to prove the uniqueness of static black hole in higher dimensional asymptotically flat spacetimes. In the proof, the Penrose inequality plays a key role in higher dimensions as well as four dimensions.
Human-Related Emotional Stimuli Can Cause a Hippocampal and Thalamic Over-Response in People with Unstable Personalities  [PDF]
Yuko Mizuno-Matsumoto, Takuto Hayashi, Eika Okamoto, Daisuke Miwa, Tetsuya Asakawa, Ayumi Muramatsu, Makoto Kato, Tsutomu Murata
Journal of Behavioral and Brain Science (JBBS) , 2013, DOI: 10.4236/jbbs.2013.37053
Abstract: Hippocampus is crucial for the formation of emotional memory. We found the relationship between hippocampal responses to emotional stimuli and the mental stabilities of people in our preliminary study. In this study, we have also evaluated how the emotional stimuli would affect amygdala and thalamus in the brain, and how the personality stabilities could relate to the responses in the brain using functional magnetic resonance imaging (fMRI). We evaluated the subjects personality features with the Yatabe-Guilford Personality Test (Y-G test) and psychosomatic symptoms with the Cornell Medical Index (CMI). The subjects were categorized into the mentally stable group and the mentally unstable group according to the total scores of the Y-G test and the CMI. The brain functional responses under emotional stimuli were measured using fMRI. The region of interest (ROI) analysis was performed to abstract significant changes in order to compare responses among the different emotional stimuli. We conducted the regression analysis to abstract the relationship between the mean % signal change from fMRI and the personality stability. The fMRI results showed that the hippocampus, thalamus, and right amygdala activities under the human relationship stimuli increased with ascending value of mental instability. Our findings suggest that the memory process in the hippocampus and the threat alarm system in the thalamus under the human-related stimuli crucially influence the emotional reaction of mentally unstable people. These processes in the brain would affect the event that stresses on human relationships that often cause people to suffer from mental disorders.

Changes in reaction time, coefficient of variance of reaction time, and autonomic nerve function in the mental fatigue state caused by long-term computerized Kraepelin test workload in healthy volunteers  [PDF]
Daisuke Kuratsune, Seiki Tajima, Junichi Koizumi, Kouzi Yamaguti, Tetsuya Sasabe, Kei Mizuno, Masaaki Tanaka, Naoko Okawa, Hideki Mito, Hirokazu Tsubone, Yasuyoshi Watanabe, Masayasu Inoue, Hirohiko Kuratsune
World Journal of Neuroscience (WJNS) , 2012, DOI: 10.4236/wjns.2012.22016
Abstract: Fatigue is a common sense caused by crushing labor, stressful social events and various illnesses. It is usually judged by their subjective symptoms, but it should be evaluated in an objective perspective. Here we show that the decrease of working efficiency and sympathetic hyperactivity are associated with mental fatigue state caused by prolonged mental workload. Recently we made a new mental fatigue model of healthy volunteers caused by long-term computerized Kraepelin test (CKT) workload. CKT is our new software for automatically checking the calculation capability, with which it is easy to determine the reaction time (RT), coefficient of variance of reaction time (CV), and accuracy of the answers (AC) during tasks. We put 24 healthy volunteers into the fatigue state by subjecting them to 120 minutes’ CKT workload, and then studied the changes in fatigue sensation, RT, CV, and AC before and after the CKT workload. The fatigue sensation, RT, and CV were clearly increased by the fatigue-inducing task and recovered during the resting period. We also studied the changes in autonomic nerve activity by using heart rate variability analysis. The low/high frequency component ratio (LF/HF) was signifi-cantly increased by the fatigue-inducing task and decreased by resting, suggesting that mental stress causes a relatively sympathetic nerve activity-dominant state. Therefore, our new fatigue model involving a long-term CKT workload is a good mental fatigue model to provide much information about the fatigue state simultane-ously, and the increase of RT, CV, and proportion of sympathetic activity (LF/HF) are associated with mental fatigue state. These might be useful objective biomarkers or evaluating a mental fatigue state.
Heterogeneity and Colonial Governance  [PDF]
Nobuhiro Mizuno
Theoretical Economics Letters (TEL) , 2015, DOI: 10.4236/tel.2015.52032
Abstract: Some existing studies argue that indirect colonial rule adversely affects postcolonial development. To analyze the situation under which a colonial power adopts indirect rule to govern a colony, we analyze a delegation model wherein the colonial power decides whether to delegate policy choice to an agent who has an information advantage but has different policy preferences from that of the colonial power. The colonial power decides whether to delegate policy choice in multiple districts, and can acquire information by paying a cost in each district. We show that colonial powers are prone to adopt indirect rule when the heterogeneity among districts is high. The results are a possible explanation for why colonial powers utilized indirect rule in Africa, a region with high levels of ethnic diversity.
Early Visual Processing is Affected by Clinical Subtype in Patients with Unilateral Spatial Neglect: A Magnetoencephalography Study
Katsuhiro Mizuno,Tetsuya Tsuji,Yves Rossetti,Laure Pisella,Hisao Ohde,Meigen Liu
Frontiers in Human Neuroscience , 2013, DOI: 10.3389/fnhum.2013.00432
Abstract: Objective: To determine whether visual evoked magnetic fields (VEFs) elicited by right and left hemifield stimulation differ in patients with unilateral spatial neglect (USN) that results from cerebrovascular accident.
Optimum detection for extracting maximum information from symmetric qubit sets
Jun Mizuno,Mikio Fujiwara,Makoto Akiba,Tetsuya Kawanishi,Stephen M. Barnett,Masahide Sasaki
Physics , 2001, DOI: 10.1103/PhysRevA.65.012315
Abstract: We demonstrate a class of optimum detection strategies for extracting the maximum information from sets of equiprobable real symmetric qubit states of a single photon. These optimum strategies have been predicted by Sasaki et al. [Phys. Rev. A{\bf 59}, 3325 (1999)]. The peculiar aspect is that the detections with at least three outputs suffice for optimum extraction of information regardless of the number of signal elements. The cases of ternary (or trine), quinary, and septenary polarization signals are studied where a standard von Neumann detection (a projection onto a binary orthogonal basis) fails to access the maximum information. Our experiments demonstrate that it is possible with present technologies to attain about 96% of the theoretical limit.
Psychological characteristics of Japanese patients with chronic pain assessed by the Rorschach test
Kazumi Yamamoto, Kenji Kanbara, Hiromi Mutsuura, Ikumi Ban, Yasuyuki Mizuno, Tetsuya Abe, Maki Yoshino, Aran Tajika, Yoshihide Nakai, Mikihiko Fukunaga
BioPsychoSocial Medicine , 2010, DOI: 10.1186/1751-0759-4-20
Abstract: The Rorschach Comprehensive System was administered to 49 in-patients with non-malignant chronic pain. Major variables and frequencies from the test were then compared to normative data from non-patient Japanese adults by way of the t-test and chi-square test.Patients exhibited high levels of emotional distress with a sense of helplessness with regard to situational stress, confusion, and ambivalent feelings. These emotions were managed by the patients in an inappropriate manner. Cognitive functions resulted in moderate dysfunction in all stages. Information processing tended to focus upon minute features in an inflexible manner. Mediational dysfunction was likely to occur with unstable affective conditions. Ideation was marked by pessimistic and less effective thinking. Since patients exhibited negative self-perception, their interpersonal relationship skills tended to be ineffective. Originally, our patients displayed average psychological resources for control, stress tolerance, and social skills for interpersonal relationships. However, patient coping styles were either situation- or emotion-dependent, and patients were more likely to exhibit emotional instability influenced by external stimuli, resulting in increased vulnerability to pain.Data gathered from the Rorschach test suggested psychological approaches to support chronic pain patients that are likely to be highly beneficial, and we thus recommend their incorporation into the course of current pain treatments.The number of patients with chronic pain in Japan is estimated to be approximately 17 million [1]. Issues concerning the treatment of chronic pain, such as elevating medical expenses, inappropriate treatment measures and deteriorating quality of life for both patients and their families have resulted in immeasurable social loss, accompanied by personal and social factors associated with the aging society [2,3].Pain of any kind can be a strong impetus for patients to seek medical care as they assume
The neuroprotective effects of milk fat globule-EGF factor 8 against oligomeric amyloid β toxicity
Endong Li, Mariko Noda, Yukiko Doi, Bijay Parajuli, Jun Kawanokuchi, Yoshifumi Sonobe, Hideyuki Takeuchi, Tetsuya Mizuno, Akio Suzumura
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-148
Abstract: The release of MFG-E8 from microglia treated with conditioned medium from neurons exposed to neurotoxic substances, glutamate or oligomeric amyloid β (oAβ) was measured by ELISA. The neuroprotective effects of MFG-E8 and MFG-E8???induced microglial phagocytosis of oAβ were assessed by immunocytochemistry. The effects of MFG-E8 on the production of the anti-oxidative enzyme hemeoxygenase-1 (HO-1) were determined by ELISA and immunocytochemisty.MFG-E8 was induced in microglia treated with conditioned medium from neurons that had been exposed to neurotoxicants, glutamate or oAβ. MFG-E8 significantly attenuated oAβ-induced neuronal cell death in a primary neuron???microglia coculture system. Microglial phagocytosis of oAβ was accelerated by MFG-E8 treatment due to increased CD47 expression in the absence of neurotoxic molecule production, such as tumor necrosis factor-α, nitric oxide, and glutamate. MFG-E8???treated microglia induced nuclear factor E(2)???related factor 2 (Nrf2)???mediated HO-1 production, which also contributed to neuroprotection.These results suggest that microglia release MFG-E8 in response to signals from degenerated neurons and that MFG-E8 protects oAβ-induced neuronal cell death by promoting microglial phagocytic activity and activating the Nrf2-HO-1 pathway. Thus, MFG-E8 may have novel roles as a neuroprotectant in neurodegenerative conditions.
Fingolimod Phosphate Attenuates Oligomeric Amyloid β–Induced Neurotoxicity via Increased Brain-Derived Neurotrophic Factor Expression in Neurons
Yukiko Doi, Hideyuki Takeuchi, Hiroshi Horiuchi, Taketo Hanyu, Jun Kawanokuchi, Shijie Jin, Bijay Parajuli, Yoshifumi Sonobe, Tetsuya Mizuno, Akio Suzumura
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061988
Abstract: The neurodegenerative processes that underlie Alzheimer's disease are mediated, in part, by soluble oligomeric amyloid β, a neurotoxic protein that inhibits hippocampal long-term potentiation, disrupts synaptic plasticity, and induces the production of reactive oxygen species. Here we show that the sphingosine-1-phosphate (S1P) receptor (S1PR) agonist fingolimod phosphate (FTY720-P)-a new oral drug for multiple sclerosis-protects neurons against oligomeric amyloid β-induced neurotoxicity. We confirmed that primary mouse cortical neurons express all of the S1P receptor subtypes and FTY720-P directly affects the neurons. Treatment with FTY720-P enhanced the expression of brain-derived neurotrophic factor (BDNF) in neurons. Moreover, blocking BDNF-TrkB signaling with a BDNF scavenger, TrkB inhibitor, or ERK1/2 inhibitor almost completely ablated these neuroprotective effects. These results suggested that the neuroprotective effects of FTY720-P are mediated by upregulated neuronal BDNF levels. Therefore, FTY720-P may be a promising therapeutic agent for neurodegenerative diseases, such as Alzheimer's disease.
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