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PLCß1 null mouse, a model for epilepsy/schizophrenia, shows enhanced moving activity, seizures, and excessive neurogenesis in the DG of the hippocampus. Since physical or epileptic activity increases neurogenesis, we asked whether the increase of neurogenesis in PLCß1 null mice was mainly due to the loss of PLCß1 in stem cells or from in vivo effects of the enhanced movement or seizures of null mice. To avoid in vivo effects, we did neurosphere cultures from the DG of the adult hippocampus and quantified the cell proliferation. We found an increase in the number and size of neurospheres in KO mice cultures, which was similar to the enhancement of in vivo proliferation of DG newborn cells in KO mice. Moreover, the positive effect of high KCl treatment on the proliferation of neurosphere culture was occluded in KO mice. Further DG neurons of PLCß1 KO mice display increased excitability, consistent with a model for epilepsy. In conclusion, these results suggest cell-autonomous inhibitory roles of PLCß1 in the proliferation of adult neural stem/progenitor cells in vivo and the excitability of DG granule cells.
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Hipocampo , Neurogénesis , Ratones , Animales , Fosfolipasa C beta , Neurogénesis/fisiología , Proliferación Celular , Ratones Noqueados , Convulsiones , Giro Dentado/fisiologíaRESUMEN
Cytokines are important neuroinflammatory modulators in neurodegenerative brain disorders including traumatic brain injury (TBI) and stroke. However, their temporal effects on the physiological properties of microglia and neurons during the recovery period have been unclear. Here, using an ATP-induced cortical injury model, we characterized selective effects of ATP injection compared to needle-control. In the damaged region, the fluorescent intensity of CX3CR1-GFP (+) cells, as well as the cell density, was increased and the maturation of newborn BrdU (+) cells continued until 28 day-post-injection (dpi) of ATP. The excitability and synaptic E/I balance of neurons and the inward and outward membrane currents of microglia were increased at 3 dpi, when expressions of tumor necrosis factor (TNF)-α/interleukin (IL)-1ß and IL-10/IL-4 were also enhanced. These changes of both cells at 3 dpi were mostly decayed at 7 dpi and were suppressed by any of IL-10, IL-4, suramin (P2 receptor inhibitor) and 4-AP (K+ channel blocker). Acute ATP application alone induced only small effects from both naïve neurons and microglial cells in brain slice. However, TNF-α alone effectively increased the excitability of naïve neurons, which was blocked by suramin or 4-AP. TNF-α and IL-1ß increased and decreased membrane currents of naïve microglia, respectively. Our results suggest that ATP and TNF-α dominantly induce the physiological activities of 3 dpi neurons and microglia, and IL-10 effectively suppresses such changes of both activated cells in K+ channel- and P2 receptor-dependent manner, while IL-4 suppresses neurons preferentially.
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Lesiones Traumáticas del Encéfalo/metabolismo , Lesiones Traumáticas del Encéfalo/patología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Potenciales de la Membrana , Microglía/fisiología , Adenosina Trifosfato/metabolismo , Animales , Lesiones Traumáticas del Encéfalo/diagnóstico , Lesiones Traumáticas del Encéfalo/etiología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Expresión Génica , Genes Reporteros , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Antagonistas Purinérgicos/farmacologíaRESUMEN
INTRODUCTION: Densin-180 interacts with postsynaptic molecules including calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) but its function in learning and memory process has been unclear. METHODS: To investigate a role of hippocampal densin-180 in contextual fear conditioning (CFC) learning and memory processes, knockdown (KD) of densin-180 in hippocampal subareas was applied. RESULTS: First, ventral hippocampal (vHC) densin-180 KD impaired single-trial CFC (stCFC) memory one day later. stCFC caused freezing behaviors to reach the peak about one hour later in both control and KD mice, but then freezing was disappeared at 2 hr postshock in KD mice. Second, stCFC caused an immediate and transient reduction of vHC densin-180 in control mice, which was not observed in KD mice. Third, stCFC caused phosphorylated-T286 (p-T286) CaMKIIα to change similarly to densin-180, but p-T305 CaMKIIα was increased 1 hr later in control mice. In KD mice, these effects were gone. Moreover, both basal levels of p-T286 and p-T305 CaMKIIα were reduced without change in total CaMKIIα in KD mice. Fourth, we found double-trial CFC (dtCFC) memory acquisition and retrieval kinetics were different from those of stCFC in vHC KD mice. In addition, densin-180 in dorsal hippocampal area appeared to play its unique role during the very early retrieval period of both CFC memories. CONCLUSION: This study shows that vHC densin-180 is necessary for stCFC memory formation and retrieval and suggests that both densin-180 and p-T305 CaMKIIα at 1 ~ 2 hr postshock are important for stCFC memory formation. We conclude that roles of hippocampal neuronal densin-180 in CFC are temporally dynamic and differential depending on the pattern of conditioning stimuli and its location along the dorsoventral axis of hippocampal formation.
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Miedo , Hipocampo , Animales , Condicionamiento Clásico , Memoria , Ratones , Ratones Endogámicos C57BL , NeuronasRESUMEN
Ultralow-threshold coherent light emitters can be achieved through lasing from exciton-polariton condensates, but this generally requires sophisticated device structures and cryogenic temperatures. Polaritonic nanolasers operating at room temperature lie on the crucial path of related research, not only for the exploration of polariton physics at the nanoscale but also for potential applications in quantum information systems, all-optical logic gates, and ultralow-threshold lasers. However, at present, progress toward room temperature polariton nanolasers has been limited by the thermal instability of excitons and the inherently low quality factors of nanocavities. Here, we demonstrate room temperature polaritonic nanolasers by designing wide-gap semiconductor heterostructure nanocavities to produce thermally stable excitons coupled with nanocavity photons. The resulting mixed states of exciton polaritons with Rabi frequencies of approximately 370 meV enable persistent polariton lasing up to room temperature, facilitating the realization of miniaturized and integrated polariton systems.
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BACKGROUND Osteoprotegerin (OPG) is a soluble glycoprotein that belongs to the tumor necrosis factor (TNF) receptor superfamily. OPG is mainly secreted by bone. The relationship between acute resistance training, serum OPG levels and metabolic syndrome, including insulin resistance, remains unclear. The purpose of this study was to determine the effect of resistance exercise on serum OPG levels and insulin resistance in middle-aged women with metabolic syndrome. MATERIAL AND METHODS Twenty-four middle-aged women were divided into those with metabolic syndrome (n=12) and a normal control group without metabolic syndrome or insulin resistance (n=12). Metabolic syndrome was diagnosed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. The quantitative insulin-sensitivity check index (QUICKI) and the homeostatic model assessment (HOMA) index for assessing beta-cell function and insulin resistance were used. The intensity of the resistance exercise was 60-70% of the repetition maximum, for 40 minutes with 10-12 repetitions, performed three times per week. Venous blood samples were tested using standard laboratory procedures. RESULTS Before exercise, the metabolic syndrome group showed a significant increase in waist circumference (P=0.030) and serum triglyceride (TG) (P=0.014), and lower high-density lipoprotein-cholesterol (HDL-C) (P=0.010) compared with the control group. After the eight-week resistance exercise program, waist circumference, and the QUICKI decreased and OPG levels were significantly increased in the metabolic syndrome group compared with the normal control group. CONCLUSIONS A resistance exercise program was effective in reducing factors associated with metabolic syndrome including insulin resistance and increases serum levels of OPG in middle-aged women.
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Síndrome Metabólico/metabolismo , Síndrome Metabólico/fisiopatología , Osteoprotegerina/metabolismo , Entrenamiento de Fuerza/métodos , Glucemia , Índice de Masa Corporal , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ejercicio Físico/fisiología , Terapia por Ejercicio/métodos , Femenino , Humanos , Resistencia a la Insulina/fisiología , Síndrome Metabólico/sangre , Persona de Mediana Edad , Obesidad/sangre , Osteoprotegerina/análisis , Osteoprotegerina/sangre , Triglicéridos/sangre , Circunferencia de la CinturaRESUMEN
A diameter-modulated silicon nanowire array to enhance the optical absorption across broad spectral range is presented. Periodic shape engineering is achieved using conventional semiconductor processes and the unique optical properties are analyzed. The periodicity in the diameter of the silicon nanowires enables stronger and more closely spaced optical resonances, leading to broadband absorption enhancement.
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[Purpose] This study aims to provide information on safe walker-aided walking by analyzing elderly subjects' walking with a walker pocket of different weights attached at different locations. [Subjects and Methods] Twenty elderly right-handed males participated in the study, and a walking analyzer was used to examine their walking with a pocket attached to the left, center, and right side of the walker. The weight of the pocket was set at three levels relative to the average weight of the subject group: 0% (without pocket), 2.5% (2â kg), and 5.5% (4â kg). [Results] In terms of the pocket location, step width was the narrowest when the pocket was attached to the right side, while the other elements of walking did not change. In terms of the pocket weight, all elements of walking showed changes. A heavier pocket led to a shorter step length and stride, a greater step width, and longer time. [Conclusion] When elderly people use a pocket-attached walker, the pocket is recommended to be attached to the right side of the walker, and its weight should be kept under 5.5% of the user's weight to ensure safe walking.
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The present study investigated the regulatory mechanisms by which epigallocatechin-3-gallate (EGCG) exerts vascular endothelial growth factor (VEGF)-, p53- and AMP-activated protein kinase (AMPK)-associated pro-apoptotic and migration-suppressing effects on colon cancer cells. EGCG decreased the expression levels of VEGF and matrix metalloproteinase (MMP)-9. EGCG treatment induced apoptosis in the presence of wild-type and mutant p53, indicating that a p53-independent pathway may contribute to EGCG-induced apoptosis in these cells. EGCG showed migration-suppressing effects, suggesting that this activity may also have p53-dependent and -independent components. The interaction between p53 and VEGF in the EGCG-treated cells was investigated using pifithrin-α. Notably, the suppression of p53 activity blocked the ability of EGCG to inhibit VEGF and MMP-9 in the cells expressing wild-type p53, but not mutant p53, indicating that the effects of EGCG on VEGF may be p53-dependent or -independent. Finally, although AMPK and VEGF did not appear to co-localize, the results indicated that AMPK controls VEGF in EGCG-treated cells regardless of the p53 status.