Combination of Dasatinib and Quercetin alleviates heat stress-induced cognitive deficits in aged and young adult male mice.

OBJECTIVE: Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy. METHODS: Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed. RESULTS: Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes. CONCLUSIONS: First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gut-endotoxin axis function.

Antidepressant-like effect and phytochemical profile of supercritical CO2 extract from Citri reticulatae pericarpium.

Citri reticulatae pericarpium is a condiment, adding much flavor in Chinese food. Also it can be used to treat depression as a Traditional Chinese Medicine (TCM). The study here aimed to evaluate the antidepressant effect between the supercritical CO2 extract (SC-E) from Citri reticulatae pericarpium and the essential oil extracted by steam distillation (SD-E). And chemical compositions of SC-E were qualitatively analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and gas chromatography-mass spectrometry (GC-MS). Compared with SD-E, SC-E showed a stronger antidepressant-like effect in FST and TST mice. And it also decreased the content of monoamine oxidase (MAO) in the cerebral cortex of stressed mice. A total of 60 compounds were identified in SC-E. Among them, 28 compounds were characterized in UPLC-Q-TOF/MS analysis and all are polymethoxyflavones (PMFs). Three main compounds, 3,5,6,7,8,3',4'-heptamethoxyflavone, nobiletin and tangeretin, together account for 66.09% of the total relative peak area. 33 terpenes were identified by GC-MS analysis, such as D-limonene (12.34%), ß-elemene (8.86%), germacrene D (5.59%) and (Z, E)-α-farnesene (5.44%). Polymethoflavones and terpenes are the main constituents of SC-E responsible for its antidepressant-like effect. The study could stimulate further investigations into the antidepressant effects and mechanism of Citri reticulatae pericarpium.

Lower maternal serum 25(OH) D in first trimester associated with higher autism risk in Chinese offspring.

OBJECTIVE: The aim of this study was to examine the association between maternal serum vitamin D status in first trimester and risk of ASD at age 3-7years in the offspring. METHODS: Using a case-control design, 68 children diagnosed with ASD and 68 sex and age matched typically-developing children were included. Archived maternal blood samples from the first trimester of pregnancy (11-13weeks gestational age) were identified for those participants. Maternal serum levels of 25 hydroxyvitamin D3 [25(OH) D], unmetabolized folic acid (FA), vitamin B12, homocysteine (HCY) and High Sensitivity C Reactive protein (CRP) were measured from those samples. We examined the associations between those factors in pregnancy and diagnosis of ASD with logistic regression using SPSS. RESULTS: Mothers in autistic group had significantly lower maternal serum levels of 25(OH) D than in typically-developing group [19.2(IQR: 15.8-22.9)ng/ml vs. 24.3(19.3-27.3)ng/ml, P<0.001], with 55.9% and 29.4% being vitamin D deficient, respectively (P<0.001). Levels of 25(OH) D increased with decreasing severity of ASD as defined by the CARS score (r=-0.302, P<0.001). Maternal first trimester serum levels of 25(OH) D in the lower 3 quartiles (quartile 1, 2, 3) (compared to the highest quartile) was associated with increased odds of ASD diagnosis in offspring [OR (95% CI) Q1: 1.36(0.84-2.58, P=0.25); Q2: 2.68(1.44-4.29, P=0.006); Q3:3.99(2.58-7.12, P<0.001)]. CONCLUSIONS: Lower first trimester maternal serum levels of 25(OH) D were associated with increased risk of developing autism in offspring. If these findings are confirmed, this may present an opportunity for prenatal intervention to reduce the risk for ASD.

Role of carotid baroreflex and sympathetic responses in the push-pull effect: a simulation study.

BACKGROUND: The push-pull maneuver (PPM) can lead to loss of consciousness in pilots of high-performance aircraft. This paper presents a mathematical model for the simulation of carotid baroreflex function and sympathetic responses during PPM. METHODS: The previous model was first modified by incorporating a submodel of the carotid baroreflex and then validated by comparing the simulation results with experimental data. Then the role of the carotid baroreflex was evaluated by varying the time delay and gain of the baroreflex independently during PPM and control runs, and the influence of different PPM profiles on sympathetic efferent activities were predicted. RESULTS: Model outputs suggest that the effects of carotid baroreflex regulation with different time delays and gain factors on the push-pull effect (PPE) are almost the same as those on the control run. Meanwhile, simulation of sympathetic responses indicates that the frequency of spikes in the efferent sympathetic nerves increases with higher magnitude and longer duration of -Gz exposure, as well as with higher magnitude of +Gz exposure. However, the effect of changed sympathetic responses may be alleviated when transferred to baroreflex effectors. CONCLUSION: The simulation results support that the carotid baroreflex and sympathetic responses might have little specific influences on the PPE. It also suggests that the limited range of G alteration and transition rate should be considered when using tilting experiments to investigate sympathetic response to PPE. The limitation of the present model due to the lack of sufficient data on the contribution of different peripheral vascular beds and their myogenic response is discussed.