Hypothalamic CRF neurons facilitate brain reward function.

Aversive stimuli activate corticotropin-releasing factor (CRF)-expressing neurons in the paraventricular nucleus of hypothalamus (PVNCRF neurons) and other brain stress systems to facilitate avoidance behaviors. Appetitive stimuli also engage the brain stress systems, but their contributions to reward-related behaviors are less well understood. Here, we show that mice work vigorously to optically activate PVNCRF neurons in an operant chamber, indicating a reinforcing nature of these neurons. The reinforcing property of these neurons is not mediated by activation of the hypothalamic-pituitary-adrenal (HPA) axis. We found that PVNCRF neurons send direct projections to the ventral tegmental area (VTA), and selective activation of these projections induced robust self-stimulation behaviors, without activation of the HPA axis. Similar to the PVNCRF cell bodies, self-stimulation of PVNCRF-VTA projection was dramatically attenuated by systemic pretreatment of CRF receptor 1 or dopamine D1 receptor (D1R) antagonist and augmented by corticosterone synthesis inhibitor metyrapone, but not altered by dopamine D2 receptor (D2R) antagonist. Furthermore, we found that activation of PVNCRF-VTA projections increased c-Fos expression in the VTA dopamine neurons and rapidly triggered dopamine release in the nucleus accumbens (NAc), and microinfusion of D1R or D2R antagonist into the NAc decreased the self-stimulation of these projections. Together, our findings reveal an unappreciated role of PVNCRF neurons and their VTA projections in driving reward-related behaviors, independent of their core neuroendocrine functions. As activation of PVNCRF neurons is the final common path for many stress systems, our study suggests a novel mechanism underlying the positive reinforcing effect of stressful stimuli.

Dose-dependent action of cordycepin on the microbiome-gut-brain-adipose axis in mice exposed to stress.

The high risk for anxiety and depression among individuals with stress has become a growing concern globally. Stress-related mental disorders are often accompanied by symptoms of metabolic dysfunction. Cordycepin is a Chinese herbal medicine commonly used for its metabolism-enhancing effects. We aimed to investigate the dose-dependent effects of cordycepin on psycho-metabolic disorders induced by stress. Our behavioral tests revealed that 12.5 mg/kg cordycepin by oral gavage significantly attenuated the anxiety- and depression-like behaviors induced by stress in mice. At 25 mg/kg, cordycepin restored the reduced weight and cell size of adipose tissues caused by stress. Besides ameliorating the metabolic dysbiosis of gut microbiota due to stress, cordycepin significantly reduced the elevated contents of 5-hydroxyindoleacetic acid in the serum and prefrontal cortex at 12.5 mg/kg and reversed the decrease in adipose induced by stress at 25 mg/kg. Correlation analyses further revealed that 12.5 mg/kg cordycepin reversed stress-induced changes in the intestinal microbiome of NK4A214_group and decreased serum Myristic acid and PC(15:0/18:1(11Z)) and cytokines, such as IFN-γ and IL-1ß. 25 mg/kg cordycepin reversed stress-induced changes in the abundances of Prevoteaceae_UCG-001 and Desulfovibrio, increased serum L-alanine level, and decreased serum Inosine-5'-monophosphate level. Cordycepin thereby ameliorated the anxiety- and depression-like behaviors as well as disturbances in the adipose metabolism of mice exposed to stress. Overall, these findings offer evidence indicating that the prominent effects of cordycepin in the brain and adipose tissues are dose dependent, thus highlight the importance of evaluating the precise therapeutic effects of different cordycepin doses on psycho-metabolic diseases.

Activation of GSK-3 disrupts cholinergic homoeostasis in nucleus basalis of Meynert and frontal cortex of rats.

The cholinergic impairment is an early marker in Alzheimer's disease (AD), while the mechanisms are not fully understood. We investigated here the effects of glycogen synthase kinse-3 (GSK-3) activation on the cholinergic homoeostasis in nucleus basalis of Meynert (NBM) and frontal cortex, the cholinergic enriched regions. We activated GSK-3 by lateral ventricular infusion of wortmannin (WT) and GF-109203X (GFX), the inhibitors of phosphoinositol-3 kinase (PI3-K) and protein kinase C (PKC), respectively, and significantly decreased the acetylcholine (ACh) level via inhibiting choline acetyl transferase (ChAT) rather than regulating acetylcholinesterase (AChE). Neuronal axonal transport was disrupted and ChAT accumulation occurred in NBM and frontal cortex accompanied with hyperphosphorylation of tau and neurofilaments. Moreover, ChAT expression decreased in NBM attributing to cleavage of nuclear factor-κB/p100 into p52 for translocation into nucleus to lower ChAT mRNA level. The cholinergic dysfunction could be mimicked by overexpression of GSK-3 and rescued by simultaneous administration of LiCl or SB216763, inhibitors of GSK-3. Our data reveal the molecular mechanism that may underlie the cholinergic impairments in AD patients.

[Behavior of evolution and growth of dominant algae in the Chongqing urban section along the Three-Gorges valley].

Through sampling and analyzing algae species in natural water-body of the Yangtze river and the Jialing river located at Chongqing urban section along the Three-Gorges valley, and combining with monitoring on the influencing parameters to algae growth, such as TN/TP, light intensities and current velocities by experimental simulation, the effect on the algae propagation behavior has been studied systemically. The results show that under static hydrological condition with various TN/TP and light intensities the Chlorophyta and Cyanophyta would grow rapidly while the Bacillariophyta disappear quickly, and other algae species had little change, and the total algal cell density could exceed 10(7) cells/L. However, even if under lower current velocity as about 0.03 m/s, the total algae cell density would increase at most obviously while its density could only reach 10(6) cells/L, and the proportion of Bacillariophyta would increase with the increase of current velocity, the proportion of Chlorophyta and Cyanophyta begin decrease at same time. Apparently, evolution of the dominant algae species would take place according to the change of hydrological condition. The density of total algae is primal regressed to TN/TP and current velocities with coefficients of determination (R2) are all over 0.93 while it has lower regression coefficient with the light intensities. The samples analysis of the above two rivers under natural state also demonstrates that total algae density in the Jialing river is higher than that in the Yangtze river, and the Bacillariophyta has the absolute domination, and then are Cyanophyta and Chlorophyta, which fit in with the experimental results in our laboratory.

[Generalized behavior study on the growth dynamics for dominant algae species forming algal bloom in the three Gorges reservoir region].

From the blue-green algae species a representative algae, namely, ChloreUlla vulgaris (CV)to belong to Chlorophyta is selected as one of algae species studied in order to investigate the effect of TN, TP on the growth behavior of CV with the Monod equation, and calculate the semi-saturation constants of CV to TP(K(SP)) and TN(K(SN)). K(SN) >> K(SP) showed that the effect of TP on growth of CV is obvious significant than that of TN. The growth rate of Chlorella vulgaris is very sensitive to the concentration of phosphorus: Compares with the blank value, the special growth rate (mu) has been enhanced under the low concentration of 0.002 mg x L(-1), then the concentration turned to 0.2 mg x L(-1) the special growth rate (mu) has been enhanced obviously; but there was hardly any change under the concentration of nitrogen from 0.000 to 0.050 mg x L(-1). At the same time, in order to reveal whether there was a generalized character associating the growth dynamics of CV with that of dominant blue-green algae species, the dynamic models including CV constructed from our experimental data, dominant blue-green algae and sea algae from literature information have been compared and analyzed systemically, and the results showed that their growth dynamics behavior and ecological characteristic were extremely similar and common. According to extrapolation of the intercommunity of all growth dynamics we could describe and show availably there is a common behavior to the growth of dominant blue-green algae in the Three Gorges reservoir region. This conclusion would have some important theoretical and applied significance.

[Multi-layer model for algal growth under different behaviors of nutritious salt].

According to the fact that different behaviors of nutrition at different medium layers would make obviously different effects on rate of algal growth in water system, we established a new numerical model of the algae growth by considering these effects from various nutrition concentrations in water environment, on the surface and inside of algae cell, and especially the effect of adsorption/desorption of nutrition on the surface of algal cell. The validation of the model parameters are carried out by numerical iterative calculation with experimental data of literature, and computation results show that the mean relative error between the actual measured values cited from literature and the numerical results of this model is less than 6.9% . Furthermore, the maximum absolute values of cumulative relative error of the model and the original model which doesn't consider effect on adsorption/desorption of nutrition are 11.7% and 34.18% respectively. Obviously, the model would fit well the actual measured data. The concentration of nutrition on the surface from the model computation shows the real change status of the algae absorb nutrition under alternate condition of light/dark, and at same time, the concentration varying of ATP inside algae cell would correlate to the concentration of nutrition in water environment and to the nutrition's condition of algae cell so that the cooperating relation between molecular layer and cell layer that has theory significance has been built.

[Synergistic effects by P and N pollution to fluctuation behavior/bloom of algae along the Three-Gorges valley].

Absorption rate coefficient of algae omega(i) to nutrients such as N and P could be used for describing algal increases/decreases velocity in water areas in theory. omega(i) raise might correspond to algal quickly growth and to ccelerate absorption of N and P while omega(i) decrease might correspond to algal decompose and release of N and P. According to locale measuring data along the Three-Gorges valley and algal dynamics model of nutritious absorption we have obtained some interest 3-dimension figures in which omega(i) will varies up and down obviously with N and P concentration in special bound to show a synergistic effects of N and P that might reveal an inner behavior of algal bloom/decompose. The research results explain in reason: (1) algal blooms do will happen in one special P/N range in a certain water system; (2) when omega(1) and omega(2) ascend rapidly and simultaneously in positive direction at same time algae would bloom, and when omega(1) and omega(2) descend sharply and simultaneously in negative direction at same time algae would decompose; (3) The velocity of algal bloom is not only same approximately as one of algal decompose, but also its variety has evidently periodic fluctuation. All of these could reveal effectively mechanism of nutritious absorption/release as algal bloom/decompose.

[Relationship between algal growth and nutritious materials absorbability in the Three-Gorges Valley].

According to measuring data of various relative pollution materials such as various nitrides, phosphides and chlorophyll along the Three-Gorges valley, and with introducing a special controlling function of new strong nonlinear coupling dynamics model, in which could used to describe complex behavior and process of green algal bloom to exist in slow flow, we studied algal growth mechanism and found some strong interactions and inherence rules when N and P concentration absorbated by algae body varied with the different N and P concentration in the valley. The ratio factor (wi/cx) of the nutritious absorption coefficient of algae wi to nutritious material concentration cx not only reveals the influence relation about nutrition content absorbated by the algae at different algal concentrations, but also characterizes the some correlations between algal growth and various effects of different nutritious materials absorbated by the algae.