Depression incurs a huge personal and societal burden, impairing cognitive and social functioning and affecting millions of people worldwide. A better understanding of the biological basis of ...depression could facilitate the development of new and improved therapies. Rodent models have limitations and do not fully recapitulate human disease, hampering clinical translation. Primate models of depression help to bridge this translational gap and facilitate research into the pathophysiology of depression. Here we optimized a protocol for administering unpredictable chronic mild stress (UCMS) to non-human primates and evaluated the influence of UCMS on cognition using the classical Wisconsin General Test Apparatus (WGTA) method. We used resting-state functional MRI to explore changes in amplitude of low-frequency fluctuations and regional homogeneity in rhesus monkeys. Our work highlights that the UCMS paradigm effectively induces behavioral and neurophysiological (functional MRI) changes in monkeys but without significantly impacting cognition. The UCMS protocol requires further optimization in non-human primates to authentically simulate changes in cognition associated with depression.
•A new UCMS induces depressive-like behavior in rhesus monkeys.•fMRI signals after modeling were significantly different to controls in several brain regions.•The UCMS produced behavioral and physiological changes in monkeys, although this did not manifest as cognitive changes.
As a natural metabolite of limonoids from Dictamnus dasycarpus, fraxinellone has been reported to be neuroprotective and anti‐inflammatory. However, its influence on cellular metabolism remains ...largely unknown. In the present study, we investigated the effect of fraxinellone on cellular senescence‐induced by oxidative stress and the potential mechanism. We found that fraxinellone administration caused growth arrest and certainly repressed the activity of senescence associated β‐galactosidase as well as the expression of senescence‐associated‐genes. Interestingly, this effect of fraxinellone is closely correlated with the restoration of impaired autophagy and the activation of AMPK. Notably, fraxinellone reacts in an AMPK‐dependent but mTORC1‐independent manner. Together, our study demonstrates for the first time that fraxinellone has the effect on senescence inhibition and AMPK activation, and supports the notion that autophagic mechanism is important for aging prevention. These findings expanded the list of natural compounds and will be potentially utilized for aging decay and/or AMPK activation.
We found that fraxinellone administration caused growth arrest and certainly repressed the activity of senescence‐associated β‐galactosidase as well as the expression of senescence‐associated genes. Interestingly, this effect of fraxinellone is closely correlated with the restoration of impaired autophagy and the activation of AMPK. Notably, fraxinellone reacts in an AMPK‐dependent but mTORC1‐independent manner.
Global germ line loss of fat mass- and obesity-associated (FTO) gene results in both the reduction of fat mass and lean mass in mice. The role of FTO in adipogenesis has been proposed, however, that ...in myogenesis has not. Skeletal muscle is the main component of body lean mass, so its connection with FTO physiologic significance need to be clarified. Here, we assessed the impact of FTO on murine skeletal muscle differentiation by in vitro and in vivo experiments. We found that FTO expression increased during myoblasts differentiation, while the silence of FTO inhibited the differentiation; in addition, skeletal muscle development was impaired in skeletal muscle FTO-deficient mice. Significantly, FTO-promoted myogenic differentiation was dependent on its m6A demethylase activity. Mechanically, we found that FTO downregulation suppressed mitochondria biogenesis and energy production, showing as the decreased mitochondria mass and mitochondrial DNA (mtDNA) content, the downregulated expression of mtDNA-encoding genes and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1) gene, together with declined ATP level. Moreover, the involvement of mTOR-PGC-1 pathway in the connection between FTO and muscle differentiation is displayed, since the expression of FTO affected the activity of mTOR and rapamycin blocked FTO-induced PGC-1 transcription, along with the parallel alteration pattern of FTO expression and mTOR phosphorylation during myoblasts differentiation. Summarily, our findings provide the first evidence for the contribution of FTO for skeletal muscle differentiation and a new insight to study the physiologic significance of RNA methylation.
A 200
km-wide thermal anomaly was recorded by thermal infrared satellite data in a heavily faulted region of the South China Sea, at the time of the 1999 Chi-Chi earthquake in Taiwan. Subsurface ...data, including vitrinite reflectance data, indicate anomalously hot fluid flow in porous aquifers in the geological record for the same region. These observations link a seismic thermal anomaly to the long-term expulsion of hot fluid from a deep, overpressured aquifer.
The modeling of formation pressure in Yinggehai shows that DF1-1 diapir has oscilla-torily released thermal fluids twice since 5.0 Ma, which may be controlled by the multi-structural subsidences and ...their accompanying thermal events. Using thermal indicators of formation temperature by DST, I/S mixed clay minerals, homogeneous temperature of inorganic fluid inclusion and δ13C of methane to trace the thermal fluid migrating order and path, we found that there are two orders of natural gas migration-accumulation in the upper site over the top of the overpressured compartment. Based on the oscillatory development of formation pressure, we postulate there would exist earlier (before 5.0 Ma) gas accumulation in their deeper site.
AIM:To observe the effects of low molecular weight heparin(LMWH) on platelet surface P-selectin expression and serum interleukin-8 production in rats with trinitrobenzene sulphonic acid (TNBS) ...induced colitis.METHODS:Colitis was induced in female Sprauge-Dawley rats by colonic administration of 2, 4, 6-TNBS. LMWH, a dalteparin (150U/kg, 300U/kg) was subcutaneously administrated one hour before induction of colitis and went on once a day for 6 days. Then a half dose was given for the next 7 days. Control animals received the same volume of normal saline once a day for 14 days after treated by TNBS.Animals were sacrificed at 24h, days 7 and 14 after induction of colitis. The colon was excised for the evaluation of macroscopic and histological findings and TNF-α immunohistochemical assay. Platelet surface P-selectin expression was determined by radioimmunoassay and serum IL-8 production was assayed by ELISA method.RESULTS:LMWH treatment in a dose of 300U/kg for 14 days significantly improved colonic inflammation by histological examination. Serum IL-8 production in the 300U/kg treatment group was more significantly decreased at day 14 than that at 24h (P<0.05). However, platelet surface P-selectin expression and TNF-α staining in colonic tissue were not significantly different among the three groups.CONCLUSION:LMWH has an anti-infiammatory effect on TNBS induced colitis in rats. The effect is possibly related to inhibition of proinflammatory cytokine IL-8, but not involved platelet surface P-selectin expression.
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