细胞外信号调节蛋白激酶-cAMP反应元件结合蛋白信号通路在应激所致抑郁行为障碍中的作用

Stress is the most important factor in the vulnerability to depression and other behavioral disorders, but the mechanisms that stress signals are transferred into depression are far from understanding. To date, the neurotransmitters, neurotrophins and signal pathway have been concerned in the topic focusing on the pathophysiology of depression, but there are still many puzzles. Increasing evidence has indicated that the alteration in neuronal plasticity is the “trace” of stress-induced damages. The extracellular signal-regulated protein kinase(ERK)-cyclic-AMP-responsive element（CRE）-binding protein(CREB)signal pathway is a powerful intracellular signal transduction pathway participating in neuronal plasticity which is involved in higher brain cognitive functions such as learning and memory. However, so far, little is known about the role of the ERK-CREB signal pathway in response to stress and emotional modulations. Thus the aim of the study was to systematically investigate the role of the ERK-CEB signal pathway in depressive-like behaviors induced by stress. Depression animal models, antidepressant agent treatment and disruption of signal pathway in specific brain regions were applied. In the present study, three experiment sessions were designed to make sure whether the ERK-CREB signal pathway was indeed one of pathophysiological mechanisms of depressive-like behaviors induced by stress. In experiment one, two different stress animal models were applied, chronic forced swim stress and chronic empty water bottle stress. After stress, all animals were tested behaviorally using open-field, elevated-plus maze and saccharine preference test, and brain samples were processed for determination of ERK, P-ERK, CREB and P-CREB using western blot. The relationships between the proteins of ERK, P-ERK, CREB and P-CREB in the brain and the behavioral variables were also analyzed. In experiment two, rats were treated with antidepressant agent fluoxetine once a day for 21 consecutive days, then the brain levels of ERK, P-ERK, CREB and P-CREB was determined, the depressive-like behaviors were also examined. In experiment three, mitogen activated extracellular-signal-regulated kinase kinase (MEK) inhibitor U0126 was administrated to inhabit the activation of ERK in the hippocampus and prefrontal cortex respectively, then behavioral measurements and protein detection were conducted. The main results of the study were as the following: (1) Chronic forced swim stress induced animals to suffer depression and disrupted the ERK-CREB signal pathway in hippocampus and prefrontal cortex. There were significant correlations between P-ERK2, P-CREB and multiple variables of depressive-like behaviors. (2) Chronic empty water bottle stress did not induce depressive-like behaviors. Such stress decreased the brain level of P-ERK2 in hippocampus and prefrontal cortex, but the level of P-CREB in the hippocampus was increased. (3) The antidepressant agent fluoxetine relieved depressive-like behaviors and increased the activities of the ERK-CREB signal pathway in stressed animals. (4) Animals treated with U0126 injection into hippocampus showed decreased activities of the ERK-CREB signal pathway in the hippocampus, and suffered depression comorbid with anxiety. (5) Animals treated with U0126 injection into prefrontal cortex showed decreased activities of the ERK-CREB signal pathway in the prefrontal cortex, and exhibited depressive-like behaviors. In conclusion, The ERK-CREB signal pathway in the hippocampus and prefrontal cortex was involved in stress responses and significantly correlated with depressive-like behaviors; The ERK-CREB signal pathway in the hippocampus and prefrontal cortex participated in the mechanism that fluoxetine reversed stress-induced behavioral disorders, and might be the target pathway of the therapeutic action of antidepressants; The disruption of the ERK-CREB signal pathway in the hippocampus or prefrontal cortex led to depressive-like behaviors in animals, suggesting that disruption of ERK-CREB pathway in the hippocampus or prefrontal cortex was involved in the pathophysiology of depression, and might be at least one of the mechanisms of depression induced by stress.

Dynamic stress intensity factor of a functionally graded material under antiplane shear loading

The dynamic response of a finite crack in an unbounded Functionally Graded Material (FGM) subjected to an antiplane shear loading is studied in this paper. The variation of the shear modulus of the functionally graded material is modeled by a quadratic increase along the direction perpendicular to the crack surface. The dynamic stress intensity factor is extracted from the asymptotic expansion of the stresses around the crack tip in the Laplace transform plane and obtained in the time domain by a numerical Laplace inversion technique. The influence of graded material property on the dynamic intensity factor is investigated. It is observed that the magnitude of dynamic stress intensity factor for a finite crack in such a functionally graded material is less than in the homogeneous material with a property identical to that of the FGM crack plane.

Stress intensity factor histories of a steadily propagating crack under 3-D combined mode traction

Elastodynamic stress intensity factor histories of an unbounded solid containing a semi-infinite plane crack that propagates at a constant velocity under 3-D time-independent combined mode loading are considered. The fundamental solution, which is the response of point loading, is obtained. Then, stress intensity factor histories of a general loading system are written out in terms of superposition integrals. The methods used here are the Laplace transform methods in conjunction with the Wiener-Hopf technique.

Elastodynamic stress intensity factor history for a semi-infinite crack under three-dimensional transient loading

The dynamic stress intensity factor history for a semi-infinite crack in an otherwise unbounded elastic body is analyzed. The crack is subjected to a pair of suddenly-applied point loadings on its faces at a distance L away from the crack tip. The exact expression for the mode I stress intensity factor as a function of time is obtained. The method of solution is based on the direct application of integral transforms, the Wiener-Hopf technique and the Cagniard-de Hoop method. Due to the existence of the characteristic length in loading this problem was long believed a knotty problem. Some features of the solutions are discussed and graphical result for numerical computation is presented.

A new method of measuring the waveguide dispersion factor and the thermo-optic coefficient of long-period fiber gratings

Based on the Mach-Zehnder effect between the core mode and the cladding modes, the interference fringes are formed by a pair of cascaded long-period fiber gratings (CLPFGs). Theoretical analyses show that the spectral spacing and the wavelength of these fringes are functions of the waveguide dispersion factor gamma, which is a characterizing parameter to LPFG and with theoretical and applicational significance. By measuring the characteristics of the transmission spectra of CLPFGs, the absolute value of gamma can be obtained. At the same time, the thermo-optic coefficient of effective refractive index difference between core and cladding modes, p, can also be obtained by measured the temperature sensitivity of these fringes. In the experiments, \gamma\ and mu were measured by this method to be 0.874 and 4.08 x 10(-5) degreesC(-1), respectively, for LPFGs with period of 450 mum and with a HE14 resonant peak at 1554 nm. (C) 2004 Elsevier B.V. All rights reserved.

Anomalous scattering factor determined by semicircle fitting near the K-absorption edge of Ge

It is shown that the locus of the f' + if '' plot in the complex plane, f' being determined from measured f '' by using the dispersion relation, looks like a semicircle very near the absorption edge of Ge. The semicircular locus is derived from a quantum theory of X-ray resonant scattering when there is a sharp isolated peak in f '' just above the K-absorption edge. Using the semicircular behavior, an approach is proposed to determine the anomalous scattering factors in a crystal by fitting known calculated values based on an isolated-atom model to a semicircular focus. The determined anomalous scattering factors f' show excellent agreement with the measured values just below the absorption edge. In addition, the phase determination of a crystal structure factor has been considered by using the semicircular behavior.

Far-field intensity distribution and M-2 factor of hollow Gaussian beams

The far-field intensity distribution of hollow Gaussian beams was investigated based on scalar diffraction theory. An analytical expression of the M-2 factor of the beams was derived on the basis of the second-order moments. Moreover, numerical examples to illustrate our analytical results are given. (c) 2005 Optical Society of America.

Far-field intensity distribution, M-2 factor of beams generated by Gaussian mirror resonator

We investigated M-2 factor and far-field distribution of beams generated by Gaussian mirror resonator. And we found usable analytical expressions of the M2 factor and the far-field distribution intensity with respect to variation of diffraction parameters. Particular attention was paid to the parameters such as mirror spot size and reflectance of the Gaussian mirror. (c) 2006 Elsevier GrnbH. All rights reserved.