Sex-Specific Effects of Prenatal Stress on Bdnf Expression in Response to an Acute Challenge in Rats : a Role for Gadd45β

Exposure to early adversities represents a major risk factor for psychiatric disorders. We have previously shown that exposure to prenatal stress (PNS) in rats alters the developmental expression of brain-derived neurotrophic factor (Bdnf) with a specific temporal profile. However, exposure to early-life stress is known to alter the ability to cope with challenging events later in life, which may contribute to the enhanced vulnerability to stress-related disorders. Since Bdnf is also an important player for activity-dependent plasticity, we investigated whether the exposure to PNS in rats could alter Bdnf responsiveness to an acute challenge at adulthood. We found that exposure to PNS produces significant changes in Bdnf responsiveness with brain region- and gender-specific selectivity. Indeed, exposure to an acute stress upregulates Bdnf expression in the prefrontal cortex, but not in the hippocampus, of control animals. Moreover, such modulatory activity is selectively impaired in PNS female rats, an effect that was associated with changes in the modulation of the DNA demethylase Gadd45\u3b2. Our results suggest that exposure to PNS may reprogram gene transcription through epigenetic mechanisms reducing the ability to cope under adverse conditions, a trait that is disrupted in psychiatric diseases

Natural products improve healthspan in aged mice and rats: a systematic review and meta-analysis

Over the last decades a decrease in mortality has paved the way for late onset pathologies such as cardiovascular, metabolic or neurodegenerative diseases. This evidence has led many researchers to shift their focus from researching ways to extend lifespan to finding ways to increase the number of years spent in good health; “healthspan” is indeed the emerging concept of such quest for ageing without chronic or disabling diseases and dysfunctions. Regular consumption of natural products might improve healthspan, although the mechanisms of action are still poorly understood. Since preclinical studies aimed to assess the efficacy and safety of these compounds are growing, we performed a systematic review and meta-analysis on the effects of natural products on healthspan in mouse and rat models of physiological ageing. Results indicate that natural compounds show robust effects improving stress resistance and cognitive abilities. These promising data call for further studies investigating the underlying mechanisms in more depth

Anchored phosphatases modulate glucose homeostasis.

Endocrine release of insulin principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic β-cells involves ion channels and mobilization of Ca(2+) and cyclic AMP (cAMP) signalling pathways. Whole-animal physiology, islet studies and live-β-cell imaging approaches reveal that ablation of the kinase/phosphatase anchoring protein AKAP150 impairs insulin secretion in mice. Loss of AKAP150 impacts L-type Ca(2+) currents, and attenuates cytoplasmic accumulation of Ca(2+) and cAMP in β-cells. Yet surprisingly AKAP150 null animals display improved glucose handling and heightened insulin sensitivity in skeletal muscle. More refined analyses of AKAP150 knock-in mice unable to anchor protein kinase A or protein phosphatase 2B uncover an unexpected observation that tethering of phosphatases to a seven-residue sequence of the anchoring protein is the predominant molecular event underlying these metabolic phenotypes. Thus anchored signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated phosphatase activity

Morc1 knockout evokes a depression-like phenotype in mice

Morc1 gene has recently been identified by a DNA methylation and genome-wide association study as a candidate gene for major depressive disorder related to early life stress in rodents, primates and humans. So far, no transgenic animal model has been established to validate these findings on a behavioral level. In the present study, we examined the effects of a Morc1 loss of function mutation in female C57BL/6N mice on behavioral correlates of mood disorders like the Forced Swim Test, the Learned Helplessness Paradigm, O-Maze and Dark-Light-Box. We could show that Morc1(-/-) mice display increased depressive-like behavior whereas no behavioral abnormalities regarding locomotor activity or anxiety-like behavior were detectable. CORT plasma levels did not differ significantly between Morc1(-/-) mice and their wildtype littermates, yet - surprisingly - total Bdnf mRNA-levels in the hippocampus were up-regulated in Morc1(-/-) animals. Although further work would be clarifying, Morc1(-/-) mice seem to be a promising epigenetically validated mouse model for depression associated with early life stress

Trehalose administration in C57BL/6N old mice affects healthspan improving motor learning and brain anti-oxidant defences in a sex-dependent fashion: a pilot study

Aim of this study was to characterize the effects of oral trehalose administration (2%w/v) on healthspan in old mice. Trehalose was administered in drinking water for 1 month to male and female C57BL/6N mice aged 25-months. After behavioral phenotyping (grip strength, beam walking and rotarod tests), autophagy (LC3-II/actin) and oxidative stress were tested in the cerebral cortex and gastrocnemius muscle. The latter parameter was indirectly assessed by evaluating carbonyl groups added to proteins as a result of oxidative reactions, in addition to central levels of NRF2 protein, a transcription factor that regulates the expression of antioxidant enzymes. In comparison with sex-matched controls, trehalose-treated males performed better in motor planning and coordination tasks. This behavioral phenotype was associated with an activation of the ubiquitin-proteasome system, autophagy and antioxidant defences in cerebral cortex. Independently from trehalose administration, females were characterized by better motor performance and showed higher levels of ubiquitinated proteins and NRF2 in cerebral cortex, suggesting an up-regulation of basal antioxidant defences. In conclusion, trehalose was effective in counteracting some aspects of age-related decay, with specific effects in male and female subjects

Use of infrared thermography (IRT) in equine assisted interventions: physiological aspects

Infrared imaging thermography (IRT) is a technique widely used in wildlife studies and the assessment of animal welfare is among its fields of application. The heat emitted from superficial capillaries changes as blood flow is under control of the autonomic nervous system. For this reason, cutaneous temperature on selected areas can be considered as a good indicator of the health status and welfare of a particular individual. These changes in heat emitted can be quantified using IRT. The system consists of an infrared camera FLIR A65 (640 512 pixel, uncooled microbolometer detector, thermal sensitivity 0.05 \ub0C) with a 7\ub0 and 13\ub0 angle of view germanium tele lenses and a dedicated laptop. In the case of chimpanzees\u2019 studies, most of the available data derive from subjects kept in small enclosures, with little ecological validity. The aim of this research was to develop an infrared method allowing the acquisition of thermographic videos and images of animals at long distance. The system was tested on a group of eleven chimpanzees, in semi-natural conditions, housed at Parco Natura Viva in Bussolengo (Verona). The study ran between April and December 2016. Images and videos were shot at distance greater than 10 meters, during the everyday chimpanzees\u2019 life. The accuracy and repeatability of measurements was that typically reserved to the image acquisition with closer subjects at indoor conditions. Through this system it was possible to detect temperature variations in face layers by distinguishing the facial features of the subject. Thus, despite the distance from the animals, thanks to the good resolution of the system, the cutaneous temperatures were detected. In conclusion, IRT could be able to non-invasively detect different autonomic responses of the chimpanzees to different situations, suggesting that this system could be a valuable tool to study the chimpanzee\u2019s behavior and welfare at long distance

Association Between Multiparametric Magnetic Resonance Imaging of the Prostate and Oncological Outcomes after Primary Treatment for Prostate Cancer: A Systematic Review and Meta-analysis

CONTEXT: The diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) for prostate cancer (PCa) diagnosis has been extensively explored. Little is known about the prognostic value of mpMRI suspicion scores and other quantitative mpMRI information. OBJECTIVE: To systematically review the current literature assessing the relationship between pretreatment mpMRI and oncological outcomes after primary treatment for PCa to assess the role of mpMRI as a prognostic tool. EVIDENCE ACQUISITION: A computerized bibliographic search of MEDLINE/PubMed, EMBASE, Scopus, and the Cochrane Library CENTRAL databases was performed for all studies assessing the relationship between mpMRI and oncological outcomes after primary treatment for PCa. The review protocol is registered in the PROSPERO database (CRD42020209899). EVIDENCE SYNTHESIS: A total of six studies were included. Reliable evidence is still limited in this field. The Prostate Imaging-Reporting and Data System (PI-RADS) score was an independent predictor of biochemical recurrence (BCR) after radical prostatectomy (RP) in the majority of the studies included. The tumor volume at mpMRI was not significantly associated with BCR after RP for PCa. Data on disease progression and PCa-specific mortality are limited. Heterogeneity among the studies was substantial. CONCLUSIONS: The review shows that PI-RADS scores provide information on the future likelihood of cancer recurrence or progression, at least for men undergoing RP. We are of the view that this information should be taken into account to identify men at higher risk of unfavorable outcomes. PATIENT SUMMARY: A higher Prostate Imaging-Reporting and Data System score for magnetic resonance imaging of the prostate seems to be positively associated with oncological failure in prostate cancer and should be incorporated into future risk models

Ion-pairing chromatography and amine derivatization provide complementary approaches for the targeted LC-MS analysis of the polar metabolome.

Liquid chromatography coupled to mass spectrometry is a key metabolomics/metabonomics technology. Reversed-phase liquid chromatography (RPLC) is very widely used as a separation step, but typically has poor retention of highly polar metabolites. Here, we evaluated the combination of two alternative methods for improving retention of polar metabolites based on 6-aminoquinoloyl-N-hydroxysuccinidimyl carbamate derivatization for amine groups, and ion-pairing chromatography (IPC) using tributylamine as an ion-pairing agent to retain acids. We compared both of these methods to RPLC and also to each other, for targeted analysis using a triple-quadrupole mass spectrometer, applied to a library of ca. 500 polar metabolites. IPC and derivatization were complementary in terms of their coverage: combined, they improved the proportion of metabolites with good retention to 91%, compared to just 39% for RPLC alone. The combined method was assessed by analyzing a set of liver extracts from aged male and female mice that had been treated with the polyphenol compound ampelopsin. Not only were a number of significantly changed metabolites detected, but also it could be shown that there was a clear interaction between ampelopsin treatment and sex, in that the direction of metabolite change was opposite for males and females

Hippocampus-related effects of fluoxetine treatment under stressful vs enriched conditions

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