Neuroprotective effect of aloe emodin against Huntington's disease-like symptoms in R6/1 transgenic mice.

Aloe emodin is a natural anthraquinone derived from aloe or rhubarb, showing anti-renal fibrosis, anti-atherosclerosis and anti-cancer effects. Aloe emodin also shows neuroprotective effects in ischemic stroke rats. Naturally, anthraquinone derivatives generally have the effect of inhibiting the transforming growth factor-ß1 (TGF-ß1) pathway. There is an increase in the calcium/calmodulin-dependent protein kinase II (CaMKII) and TGF-ß1 levels in both Huntington's disease (HD) patients' brains and HD transgenic mice. Thus, we hypothesized that aloe emodin may inhibit the phosphorylation of CaMKII (p-CaMKII) and TGF-ß1/sma- and mad-related protein (Smad) signaling in the brain, further preventing motor and cognitive dysfunction. Aloe emodin was orally administered to 10- to 20-week-old HD R6/1 transgenic mice. Aloe emodin improved the motor coordination of R6/1 transgenic mice in the rotarod test and attenuated visual recognition impairment in the novel object recognition test. Aloe emodin downregulated levels of the mutant huntingtin protein, p-CaMKII and TGF-ß1, but not the TGF-ß2 or TGF-ß3 levels, in the brains of R6/1 mice. Aloe emodin could also inhibit neuronal apoptosis in the hippocampus of R6/1 mice. Altogether, these results indicated that aloe emodin prevents several HD-like symptoms through the inhibition of CaMKII/Smad and TGF-ß1/Smad signaling in mice.

Sodium propionate improves cognitive and memory function in mouse models of Alzheimer's disease.

This study was designed to explore whether sodium propionate (SP) alleviates cognitive damage in a mouse model of Alzheimer's disease (AD). We evaluated behavioral and biochemical aspects in an animal model of AD made by intracerebroventricular injection of Aß1-42 peptide. Two-month-old ICR mice were treated with SP or normal saline for 21 days (control group, Aß1-42 group, Aß1-42 + SP50 mg/kg group, Aß1-42 + SP100 mg/kg group, and Aß1-42 + SP200 mg/kg group). Behavioral tests showed that SP alleviated cognitive and memory impairments in AD mice. Moreover, SP treatment significantly suppressed the level of inducible nitric oxide synthase (iNOS) in the hippocampus. Concomitantly, the overexpression of interleukin-1α (IL-1α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) in the hippocampus induced by Aß1-42 was significantly reduced following treatment with SP. In addition, SP was able to increase the levels of synaptophysin (SYN) and postsynaptic dense protein 95 (PSD95). Our study shows that SP could significantly improve Aß1-42-induced spatial learning and memory impairment by reducing neuroinflammation via inhibition of proinflammatory cytokines and iNOS activation and restoring synapse plasticity by increasing synaptically associated protein levels, suggesting that SP has a positive effect and potential for AD therapies.

Silibinin Ameliorates Formaldehyde-Induced Cognitive Impairment by Inhibiting Oxidative Stress.

Silibinin is a flavonoid extracted from the medicinal plant Silybum marianum (milk thistle), traditionally used to treat liver disease. Recent studies have shown that the antioxidative stress and anti-inflammatory effects of milk thistle are used in the treatment of neurological diseases. Silibinin has antioxidative stress and antiapoptotic effects and reduces cognitive impairment in models of Alzheimer's disease (AD). However, the underlying mechanism of silibinin related to improvement of cognition remains poorly understood. In this study, we used the model of lateral ventricle injection of formaldehyde to examine the related mechanism of silibinin in improving cognitive impairment disorders. Oral administration of silibinin for three weeks significantly attenuated the cognitive deficits of formaldehyde-induced mice in a Y-maze test and Morris water maze test. Y-maze results show that silibinin increases the rate of spontaneous response alternation in FA-induced mice. Silibinin increases the target quadrant spending time and decreases escape latency in the Morris water maze test. We examined the effect of silibinin on the NRF2 signaling pathway, and silibinin promoted the nuclear transfer of NRF2 and increased the expression of HO-1 but did not significantly increase the protein expression of NRF2 in the hippocampus. Well, silibinin reduces the content of DHE and decreases the levels of apoptosis of mature neuron cells. We investigated the effect of silibinin on the content of formaldehyde degrading enzymes; biochemical analyses revealed that silibinin increased GSH and ALDH2 in formaldehyde-induced mice. In addition, as one of the pathological changes of AD, TAU protein is also hyperphosphorylated in FA model mice. Silibinin inhibits the expression of GSK-3ß in model mice, thereby reducing the phosphorylation of TAU proteins ser396 and ser404 mediated by GSK3ß. Based on our findings, we verified that the mechanism of silibinin improving cognitive impairment may be antioxidative stress, and silibinin is one of the potentially promising drugs to prevent formaldehyde-induced cognitive impairment.

Verification of a multi-function closed maze for the detection of affective disorder and spatial cognitive impairment in post-weaning socially isolated rats.

OBJECTIVE: To verify a behavioral device for the detection of learning, memory, and affective disorders in post-weaning socially isolated rats. METHODS: We tested the behavioral changes in post-weaning socially isolated rats using a multi-function closed maze, a self-developed behavioral device, against the classical mood disorder detection method, the IntelliCage system and Morris water maze. RESULTS: In the multifunctional closed maze experiment, the spatial learning and memory ability of post-weaning socially isolated rats decreased, which was consistent with the results of the water maze and IntelliCage system. Furthermore, the behavioral changes in the post-weaning socially isolated rats in the multi-function closed maze test were the same as those of the forced swimming and open field tests, indicating that the rats had depression- and anxiety-like behaviors. CONCLUSION: A multi-function closed maze can detect emotional changes, spatial learning ability, and memory ability.

Absorption coefficient of water vapor across atmospheric troposphere layer.

Absorption coefficient of water vapor proposed to be responsible for an increase in temperature in the troposphere layer with altitude less than 10 km is systematically presented in this work. Since global warming plays an important role in affecting the human life, a confirmative and detailed study of global warming is essentially need. Solar irradiation within short wavelength range can be extinguished from absorption and scattering by the atmosphere, and absorbed and reflected by the Earth's surface. Radiative within high wavelength range from the Earth's surface can be absorbed by atmospheric water vapor, carbon dioxide and other gases. The difference in solar irradiation and energy escaped to the space from the atmosphere results in the atmosphere acting as the glass of a greenhouse and increase atmospheric temperature. Extending the previous work [1] for predicting absorption coefficient of carbon dioxide through the troposphere, this work further determines absorption coefficients of water vapor in different wavelength bands centered at 71, 6.3, 2.7, 1.87 and 1.38 µ m across the temperature, pressure and concentration-dependent troposphere layer. Solving one-dimensional unsteady heat conduction-radiation equation with the COMSOL computer code, the predicted temperature together with water vapor density for different optical path lengths can be used to interpret in details absorption coefficient or the ratio between band intensity and effective band width by using the exponential wide band model. The results show that absorption coefficients are strongly affected by water vapor concentration. For example, absorption coefficients in the band centered at 71 µ m increases from 0.3 to 1.2 m - 1 at the tropopause and 0.6 to 3.1 m - 1 at the Earth's surface as mole fraction of water vapor increases from 0.005 to 0.02. The predicted absorption coefficients agree with experimental and theoretical results in the literature. A more detailed and realistic temperature profile through the troposphere with optical path length of 10 4 m is presented.

Absorption coefficient of carbon dioxide across atmospheric troposphere layer.

Absorption coefficient affected by carbon dioxide concentration and optical path length responsible for temperature or global warming across the troposphere layer, which is less than the altitude of 10 km in the atmosphere, is systematically presented in this work. Solar irradiation within a short wavelength range can be absorbed, scattered and transmitted by the atmosphere, and absorbed and reflected by the Earth's surface. Radiative emission in high wavelength ranges from the Earth's surface at low temperature can be absorbed by atmospheric water vapor, carbon dioxide and other gases. Unbalance of radiation thus results in the atmosphere to act as the glass of a greenhouse and increase atmospheric temperature. Even though global warming strongly affects the life of the human being, the cause of global warming is still controversial. This work thus proposes a fundamental and systematical unsteady one-dimensional heat conduction-radiation model together with exponential wide band model to predict absorption coefficients affected by concentration, temperature, optical path lengths and radiation correlated parameters in different bands centered at 15, 4.3, 2.7, and 2 µm of carbon dioxide across the troposphere layer. It shows that absorption coefficient required for calculating heat transfer is strongly affected by carbon dioxide concentration and optical path length across the troposphere. Relevant values of the latter should be greater than 5,000 m. Absorption coefficients in the band centered at 4.3 µm subject to a chosen optical path length of 10 4 m increase from 0.04 m-1 and 0.165 m-1at the tropopause to 0.11 m-1 and 0.44 m-1 at the Earth's surface for carbon dioxide concentrations of 100 and 400 ppm, respectively. A more relevant and detailed temperature profile across the troposphere is presented.