312 research outputs found

    NMR relaxation of quantum spin chains in magnetic fields

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    We investigate NMR relaxation rates 1/T_1 of quantum spin chains in magnetic fields. Universal properties for the divergence behavior of 1/T_1 are obtained in the Tomonaga-Luttinger-liquid state. The results are discussed in comparison with experimental results.Comment: 5 pages, 3 figure

    Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats

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    The functional role of serotonergic projections from the median raphe nucleus (MRN) to the dorsal hippocampus (DH) in anxiety remains understood poorly. The purpose of the present research was to examine the functional role of this pathway, using the contextual fear conditioning (CFC) model of anxiety. We show that intra-MRN microinjection of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduced freezing in CFC without affecting general motor activity dose-dependently, suggesting an anxiolytic-like effect. In addition, intra-MRN microinjection of mirtazapine dose-dependently increased extracellular concentrations of serotonin (5-HT) but not dopamine in the DH. Importantly, intra-DH pre-microinjection of WAY-100635, a 5-HT1A antagonist, significantly attenuated the effect of mirtazapine on freezing. These results, for the first time, suggest that activation of the MRN-DH 5-HT1A pathway exerts an anxiolytic-like effect in CFC. This is consistent with the literature that the hippocampus is essential for retrieval of contextual memory and that 5-HT1A receptor activation in the hippocampus primarily exerts an inhibitory effect on the neuronal activity

    Acupuncture Improves Sleep Conditions of Minipigs Representing Diurnal Animals through an Anatomically Similar Point to the Acupoint (GV20) Effective for Humans

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    Acupuncture, an alternative medicine, has been widely applied for people with sleep disturbances; therefore, the effects should be evaluated objectively. Micro-minipigs (MMPigs), the smallest miniature pigs for animal experiments, were used. Acupuncture was performed at two different points: Dafengmen is located on the head and is an anatomically similar point to human-Baihui (GV20), an effective acupoint for sleep disturbances in humans; pig-Baihui is on the back. The procedure was performed as follows: shallow, within 5 mm depth for several seconds; deep, 10–20 mm depth for 20 min. The sleep conditions were evaluated by actigraph, and the amount of catecholamine in pooled urine after acupuncture treatment. MMPigs with deep acupuncture at Dafengmen showed significantly efficient values on actigraph and catecholamine analysis as compared with untreated MMPigs. The effective acupoint for sleep conditions in the porcine model is at an anatomically similar point to humans, rather than the point determined by traditional Chinese medicine

    SAK3 Administration Improves Spine Abnormalities and Cognitive Deficits in AppNL-G-F/NL-G-F Knock-in Mice by Increasing Proteasome Activity through CaMKII/Rpt6 Signaling

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    Alzheimer’s disease (AD) is the most common form of dementia and is characterized by neuropathological hallmarks consisting of accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFT). Recently, we have identified a new AD therapeutic candidate, ethyl-8′-methyl-2′,4-dioxo-2-(piperidin-1-yl)-2′H-spiro[cyclopentane-1,3′-imidazo [1,2-a] pyridin]-2-ene-3-carboxylate (SAK3), which ameliorates the AD-like pathology in AppNL-F/NL-F knock-in mice. However, the detailed mechanism underlying the therapeutic effects of SAK3 remains unclear. In this study, we found that SAK3 administration improved the reduced proteasome activity through the activation of CaMKII/Rpt6 signaling in AppNL-F/NL-F knock-in (NL-G-F) mice. Moreover, spine abnormalities observed in NL-G-F mice were significantly reversed by SAK3 administration. Along with this, cognitive impairments found in NL-G-F mice were markedly ameliorated by SAK3. In summary, our data suggest that SAK3 administration increases the activity of the proteasome via activation of the CaMKII/Rpt6 signaling pathway, contributing to improvements in spine abnormalities and cognitive deficits in NL-G-F mice. Overall, our findings suggest that SAK3 might be a new attractive drug candidate, representing a new mechanism for the treatment of AD pathology

    Expression of nampt in hippocampal and cortical excitatory neurons is critical for cognitive function

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    Nicotinamide adenine dinucleotide (NAD(+)) is an enzyme cofactor or cosubstrate in many essential biological pathways. To date, the primary source of neuronal NAD(+) has been unclear. NAD(+) can be synthesized from several different precursors, among which nicotinamide is the substrate predominantly used in mammals. The rate-limiting step in the NAD(+) biosynthetic pathway from nicotinamide is performed by nicotinamide phosphoribosyltransferase (Nampt). Here, we tested the hypothesis that neurons use intracellular Nampt-mediated NAD(+) biosynthesis by generating and evaluating mice lacking Nampt in forebrain excitatory neurons (CaMKIIαNampt(−/−) mice). CaMKIIαNampt(−/−) mice showed hippocampal and cortical atrophy, astrogliosis, microgliosis, and abnormal CA1 dendritic morphology by 2–3 months of age. Importantly, these histological changes occurred with altered intrahippocampal connectivity and abnormal behavior; including hyperactivity, some defects in motor skills, memory impairment, and reduced anxiety, but in the absence of impaired sensory processes or long-term potentiation of the Schaffer collateral pathway. These results clearly demonstrate that forebrain excitatory neurons mainly use intracellular Nampt-mediated NAD(+) biosynthesis to mediate their survival and function. Studying this particular NAD(+) biosynthetic pathway in these neurons provides critical insight into their vulnerability to pathophysiological stimuli and the development of therapeutic and preventive interventions for their preservation

    Expression of Ascorbate Peroxidase Derived from Cyanidioschyzon merolae in Mammalian Cells

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    Background: Ascorbate peroxidase (APX) derived from Cyanidioschyzon merolae, a primitive red alga living in high temperature and acidic environments, has a greater anti-oxidative capacity than similar peroxidases occurring in other plants. In the present study, we examined the ability of Cyanidioschyzon merolae-derived APX (cAPX) to increase anti-oxidative capacity when expressed in mammalian cells. Materials and Methods: The cAPX gene was introduced into the mouse fibroblast-like cell line C3H10T1/2. Production of reactive oxygen species (ROS) and/or cell viability was assessed after heat, H2O2 and acid stimulation. Results: Heat and H2O2 stimulation caused ROS production. cAPX-expressing cells were more tolerant to oxidative stress induced by heat, H2O2 and acid stimulations than control cells lacking cAPX. Conclusion: Introduction of cAPX increases anti-oxidative capacity in mammalian cells

    Impacts of Sociocultural Condition on Regional Endemics of HTLV-1 and HBV among Islands in Southwestern Japan

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    The transmission pathways of two oncogenic viruses, human Tlymphotropic virus type 1 (HTLV-1) and hepatitis B virus (HBV) are very similar : maternal, sexual and by transfusion. Furthermore, individuals infected with these viruses become lifelong virus carriers. Both of these viruses are known to be endemic in Nagasaki. In trying to correlate the endemicity of these viruses with the sociocultural attributes, such as birth place, religion, sex and age, we surveyed residents (2262 in total) aged over 40 years, in three islands of Nagasaki. Markers included anti-HTLV-1 antibody and HBV related markers (HBsAg/HBsAb) in sera. The prevalences of people infected with HTLV-1 in Mishima, Narao, and Oshima were 41.1, 29.3 and 12.9 %, respectively, while those of HBV were 55.8, 35.1 and 31.7 %, respectively. HTLV-1 and HBV were endemic in all three islands. The penetrations by two viruses seemed to be correlated with each other in each island. This profile was more discrete, if we analyzed people born in the respective islands. However, the evidence to suggest the preferred coinfection of these 2 viruses could not be demonstrated. These results suggested that the intermarriage in a closed community of islands had a favorable effect to maintain the endemicity of these viruses. Christians in these islands tend to intermarry within their religion. Of males in Oshima, Christians born on the same island were significantly more anti-HTLV-1 positive than non-Christians. Similarly, male Christians of Narao and Oshima showed significantly higher prevalence of HBV markers than non-Christians. The results were consistent with the conjecture. In the case of HTLV-1, while the prevalence increased with age in both sexes in highly endemic Mishima and Narao, it remained constant in less endemic Oshima. These profiles were also seen in the subjects born in the respective islands. The age related increase of the seropositive population could hardly be explained by the dominant horizontal infections. The age independent seroprevalence in Oshima rather suggested that human factors of each island played a siginificant role for the decreased frequency of maternal infections of HTLV-1 in these several decades in the other two islands. In contrast, the prevalence of HBV markers were relatively unaffected by age except for Mishima. This suggested that the maternal infection of HBV is more efficient and dominant than that of HTLV-1. In case of Mishima, the younger female showed significantly lower prevalence

    Incommensurate state in a quasi-one-dimensional S=1/2S=1/2 bond-alternating antiferromagnet with frustration in magnetic fields

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    We investigate the critical properties of the S=1/2S=1/2 bond-alternating spin chain with a next-nearest-neighbor interaction in magnetic fields. By the numerical calculation and the exact solution based on the effective Hamiltonian, we show that there is a parameter region where the longitudinal incommensurate spin correlation becomes dominant around the half-magnetization of the saturation. Possible interpretations of our results are discussed. We next investigate the effects of the interchain interaction (JJ^{\prime}). The staggered susceptibility and the uniform magnetization are calculated by combining the density-matrix renormalization group method with the interchain mean-field theory. For the parameters where the dominant longitudinal incommensurate spin correlation appears in the case J=0J^{\prime}=0, the staggered long-range order does not emerge up to a certain critical value of JJ^{\prime} around the half-magnetization of the saturation. We calculate the static structure factor in such a parameter region. The size dependence of the static structure factor at k=2kFk=2k_{\rm F} implies that the system has a tendency to form an incommensurate long-range order around the half-magnetization of the saturation. We discuss the recent experimental results for the NMR relaxation rate in magnetic fields performed for pentafluorophenyl nitronyl nitroxide.Comment: 10 pages, 12 figures, final version, to appear in PRB vol. 70, No. 5 (2004
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