Increase Stress Resilience Research Articles

No Effects of Omega-3 Supplementation on Kynurenine Pathway, Inflammation, Depressive Symptoms, and Stress Response in Males: A Placebo-Controlled Trial.

Background: Increased inflammation and heightened physiological stress reactivity have been associated with pathophysiology of depressive symptoms. The underlying biological mechanisms by which inflammation and stress may influence neurogenesis are changes in the kynurenine (KYN) pathway, which is activated under stress. Supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) has anti-inflammatory properties and can increase stress resilience. Whether n-3 PUFAs alter KYN stress response is unknown. Objectives: This placebo-controlled study investigated the effect of n-3 PUFAs on KYN metabolism, inflammation, depressive symptoms, and mood. Moreover, stress-induced changes following a laboratory stressor have been assessed. Methods: In this placebo-controlled study, 47 healthy male adults received either 4 g n-3 PUFAs per day (Omega-3 group) or a placebo (Placebo group) for 12 weeks. Results: A significant group-by-time interaction was found for the inflammatory markers gp130 (F = 7.07, p = 0.011), IL-6R alpha (F = 10.33, p = 0.003), and TNF_RI (F= 10.92, p = 0.002). No significant group-by-time interactions were found for KYN metabolites, depressive symptoms, and mood (except for Hedonic tone (F = 6.50, p = 0.014)), nor for stress-induced changes in KYN metabolites and mood following a laboratory stressor. Conclusions: Overall, increased n-3 PUFA levels in healthy men ameliorate inflammatory markers but do not ameliorate KYN metabolism, depressive symptoms, mood, or KYN metabolism and mood following a stress induction. This study was registered at ClinicalTrials.gov with the identifier NCT05520437 (30/08/2022 first trial registration).

46 Feeding the weaned pig gut and beyond with non-nutritional additives

Abstract Weaning imposes simultaneous stress, resulting in reduced growth performance, increased susceptibility to diseases, and increased morbidity and mortality in weaned pigs. Weaning stress can induce negative changes in the intestine, including damaged intestinal integrity, disturbed digestive and absorptive capacity, increased intestinal oxidative stress, and microbial dysbiosis. Improving intestinal development and health is critically important for enhancing disease resistance and overall health of weaned pigs. This, in turn, can increase their survival rate during this vulnerable stage and improve their productive performance in later stages. A healthy gut may include, but is not limited to, several important features: a healthy proliferation of intestinal epithelial cells, an integrated gut barrier function, a preferable or balanced gut microbiota, and well-developed intestinal mucosa immunity. Burgeoning evidence suggests that many non-nutritional additives can enhance overall intestinal health and beyond by targeting one or several functions of the gut. However, the exact protective mechanisms may vary and are still not completely understood. For example, direct-fed microbials may confer health benefits on the host by producing antimicrobial products, regulating gut microbial profile or immunity, and/or enhancing gut barrier function. Non-digestible carbohydrates and prebiotics exhibit striking impacts on reshaping the composition of gut microbiota in the host by boosting the production of health-promoting bacteria. Phytochemicals, a large variety of secondary plant metabolites, have been known for their broad and promising biological properties, including anti-microbial, antioxidant, and immune-modulating activities. Several short chain fatty acids derivatives aim to target the upper gastrointestinal tract, where the major nutrients are digested and absorbed, to promote intestinal health of pigs. Moreover, butyrate and valerate glycerides exhibit strong in vitro antimicrobial effects against enterotoxigenic Escherichia coli F18, one of the dominant pathogens causing post-weaning diarrhea globally. There are more candidates in the list that have been used in weaned pigs and shown promising results on growth and health promotion. Therefore, increasing our current understanding of non-nutritional additives and their influences on intestinal function during weaning will facilitate the development of more dietary strategies that increase stress resilience of weaned pigs.

Differential Reshaping of Skin and Intestinal Microbiota by Stocking Density and Oxygen Availability in Farmed Gilthead Sea Bream (Sparus aurata): A Behavioral and Network-Based Integrative Approach.

Fish were kept for six weeks at three different initial stocking densities and water O2 concentrations (low-LD, 8.5 kg/m3 and 95-70% O2 saturation; medium-MD, 17 kg/m3 and 55-75% O2 saturation; high-HD, 25 kg/m3 and 60-45% O2 saturation), with water temperature increasing from 19 °C to 26-27 °C. The improvement in growth performance with the decrease in stocking density was related to changes in skin and intestinal mucosal microbiomes. Changes in microbiome composition were higher in skin, with an increased abundance of Alteromonas and Massilia in HD fish. However, these bacteria genera were mutually exclusive, and Alteromonas abundance was related to a reactive behavior and systemic growth regulation via the liver Gh/Igf system, while Massilia was correlated to a proactive behavior and a growth regulatory transition towards muscle rather than liver. At the intestinal level, microbial abundance showed an opposite trend for two bacteria taxa, rendering in a low abundance of Reyranella and a high abundance of Prauserella in HD fish. This trend was correlated with up-regulated host gene expression, affecting the immune response, epithelial cell turnover, and abiotic stress response. Most of the observed responses are adaptive in nature, and they would serve to infer new welfare indicators for increased stress resilience.

Specific Salivary Neuropeptides Shift Synchronously during Acute Stress in Fire Recruits.

Once thought of as an immune-privileged site, we now know that the nervous system communicates in a bidirectional manner with the immune system via the neuroimmune axis. Neuropeptides constitute a component of this axis, playing critical roles in the brain and periphery. The function of salivary neuropeptides in the acute stress response is not well understood. The purpose of this study is to investigate salivary neuropeptide levels during acute stress. Salivary samples were collected from fire recruits engaged in a stress training exercise previously shown to induce acute stress, at three separate timepoints during the exercise and levels of oxytocin, neurotensin, Substance P, α-MSH, and β-Endorphin were measured using the Human Neuropeptide 5-Plex Custom Assay Eve Technologies. All neuropeptides increased throughout the acute stress simulation and during the recovery phase. Exploratory factor analysis (EFA) identified one factor contributing to baseline values across five neuropeptides and Pairwise Pearson Correlation Coefficient analysis showed positive correlations >0.9 for almost all neuropeptide combinations at the pre-stress timepoint. Further analysis identified negative and positive correlations between past-life trauma and self-assessed hardiness, respectively. Calculated neuropeptide scores showed an overall positive correlation to self-assessed hardiness. Altogether, our results suggest that salivary neuropeptides increase synchronously during acute stress and higher levels correlate with an increase in self-assessed hardiness. Further study is required to determine if interventions designed to enhance neuropeptide activity can increase stress resilience, especially in high-stress occupations such as firefighting.

Going to the office - What’s in it for the dog?

ABSTRACT Benefits and challenges of dogs being present at the office were analyzed from three perspectives: the company view, the dog owner (employee) and the dog view. For companies, office dogs may serve as a branding symbol, leading to higher employee satisfaction and productivity, increased stress resilience and fewer turnover intentions. Yet, companies need to apply pet policies, risk management strategies and mitigate nuisance such as barking, loose fur or excrement. Additional breaks to walk the dogs are required and other employees or customers may be irritated. Employees take advantage of stress reduction, social support, higher job satisfaction, not having to leave their animal at home. Still, an office dog is an added responsibility in terms well-being, safety, distraction from work and emotional involvement. Although the animal perspective has not yet been scientifically addressed, we propose potential benefits such as less separation distress by having the owner nearby, higher social engagement and additional walks during breaks. Challenges for dogs may involve unwanted attention, aversive environmental stimulation, being restrained via leash or crate, irritation caused by conspecifics, emotional contagion or individual requirements.

Short-term heat stress assays resolve effects of host strain, repeat stress, and bacterial inoculation on Aiptasia thermal tolerance phenotypes

The ongoing loss of corals and their reef ecosystems hastens the need to develop approaches that mitigate the impacts of climate change. Given the strong reliance of corals on their associated prokaryotic and microalgal symbionts, microbiome-targeted interventions in the form of probiotics or microbiome transplants are emerging as potential solutions. Although inoculation with beneficial microorganisms was shown to improve coral bleaching recovery, the mechanistic underpinnings and extent to which microbiomes can be manipulated are largely unknown. Research progress in this regard is often hindered by coral holobiont complexity and a lack of standardized diagnostics to assess physiological and phenotypic changes following microbial manipulation. Here we address these shortcomings by establishing short-term acute thermal stress assays using the Coral Bleaching Automated Stress System (CBASS) as a standardized and reproducible experimental platform to assess stress tolerance phenotypes of the coral model Aiptasia. We show that thermal tolerance phenotypes following acute heat stress assays are highly reproducible, host species-specific, and can exert legacy effects with consequences for long-term thermal resilience. We further demonstrate the ability to resolve phenotypic differences in thermal tolerance following incubation with the coral bleaching pathogen Vibrio coralliilyticus, providing an avenue for screening bacteria for their ability to affect holobiont thermal performance. By employing acute heat stress assays in conjunction with a tractable model organism, we posit CBASS assays as a standardized experimental platform that allows functional screening for microbes that affect thermal stress tolerance. Such effort may accelerate the discovery of microbes and microbial mechanisms mediating thermal tolerance and our ability to harness them to increase stress resilience.

Tapping into the plasticity of plant architecture for increased stress resilience.

Plant architecture develops post-embryonically and emerges from a dialogue between the developmental signals and environmental cues. Length and branching of the vegetative and reproductive tissues were the focus of improvement of plant performance from the early days of plant breeding. Current breeding priorities are changing, as we need to prioritize plant productivity under increasingly challenging environmental conditions. While it has been widely recognized that plant architecture changes in response to the environment, its contribution to plant productivity in the changing climate remains to be fully explored. This review will summarize prior discoveries of genetic control of plant architecture traits and their effect on plant performance under environmental stress. We review new tools in phenotyping that will guide future discoveries of genes contributing to plant architecture, its plasticity, and its contributions to stress resilience. Subsequently, we provide a perspective into how integrating the study of new species, modern phenotyping techniques, and modeling can lead to discovering new genetic targets underlying the plasticity of plant architecture and stress resilience. Altogether, this review provides a new perspective on the plasticity of plant architecture and how it can be harnessed for increased performance under environmental stress.

Antidepressant mechanisms of ketamine: a review of actions with relevance to treatment-resistance and neuroprogression.

Concurrent with recent insights into the neuroprogressive nature of depression, ketamine shows promise in interfering with several neuroprogressive factors, and has been suggested to reverse neuropathological patterns seen in depression. These insights come at a time of great need for novel approaches, as prevalence is rising and current treatment options remain inadequate for a large number of people. The rapidly growing literature on ketamine's antidepressant potential has yielded multiple proposed mechanisms of action, many of which have implications for recently elucidated aspects of depressive pathology. This review aims to provide the reader with an understanding of neuroprogressive aspects of depressive pathology and how ketamine is suggested to act on it. Literature was identified through PubMed and Google Scholar, and the reference lists of retrieved articles. When reviewing the evidence of depressive pathology, a picture emerges of four elements interacting with each other to facilitate progressive worsening, namely stress, inflammation, neurotoxicity and neurodegeneration. Ketamine acts on all of these levels of pathology, with rapid and potent reductions of depressive symptoms. Converging evidence suggests that ketamine works to increase stress resilience and reverse stress-induced dysfunction, modulate systemic inflammation and neuroinflammation, attenuate neurotoxic processes and glial dysfunction, and facilitate synaptogenesis rather than neurodegeneration. Still, much remains to be revealed about ketamine's antidepressant mechanisms of action, and research is lacking on the durability of effect. The findings discussed herein calls for more longitudinal approaches when determining efficacy and its relation to neuroprogressive factors, and could provide relevant considerations for clinical implementation.

Screening Digitaria eriantha cv. Suvernola Endophytic Bacteria for Maize Growth Promotion.

The search for sustainable agriculture has increased interest in using endophytic bacteria to reduce fertilizer use and increase stress resilience. Stress-adapted plants are a potential source of these bacteria. Some species of these plants have not yet been evaluated for this, such as pangolão grass, from which we considered endophytic bacteria as potential plant growth promoters. Bacteria from the root, colm, leaves, and rhizospheric soil were isolated, and 132 strains were evaluated for their in vitro biological nitrogen fixation, IAA and siderophores production, and phosphate solubilization. Each mechanism was also assessed under low N availability, water stress, and low-solubility Fe and P sources in maize greenhouse experiments. All strains synthesized IAA; 63 grew on N-free media, 114 synthesized siderophores, and 46 solubilized P, while 19 presented all four mechanisms. Overall, these strains had better performance than commercial inoculant in all experiments. Still, in vitro responses were not good predictors of in vivo effects, which indicates that the former should not be used for strain selection, since this could lead to not testing strains with good plant growth promotion potential. Their heterologous growth promotion in maize reinforces the potential of stress-adapted plant species as potential sources of strains for inoculants.

Hippocampal sharp wave ripples underlie stress susceptibility in male mice

The ventral hippocampus (vHC) is a core brain region for emotional memory. Here, we examined how the vHC regulates stress susceptibility from the level of gene expression to neuronal population dynamics in male mice. Transcriptome analysis of samples from stress-naïve mice revealed that intrinsic calbindin (Calb1) expression in the vHC is associated with susceptibility to social defeat stress. Mice with Calb1 gene knockdown in the vHC exhibited increased stress resilience and failed to show the increase in the poststress ventral hippocampal sharp wave ripple (SWR) rate. Poststress vHC SWRs triggered synchronous reactivation of stress memory-encoding neuronal ensembles and facilitated information transfer to the amygdala. Suppression of poststress vHC SWRs by real-time feedback stimulation or walking prevented social behavior deficits. Taken together, our results demonstrate that internal reactivation of memories of negative stressful episodes supported by ventral hippocampal SWRs serves as a crucial neurophysiological substrate for determining stress susceptibility.

Immobilization on Polyethylenimine and Chitosan Sorbents Modulates the Production of Valuable Fatty Acids by the Chlorophyte Lobosphaera sp. IPPAS C-2047

Green microalgae, including those from the genus Lobosphaera, are exploited in various fields of biotechnology to obtain valuable fatty acids (e.g., arachidonic acid (C20:4, ARA)) for the production of infant formulae, food and feed additives. In nature, microalgae frequently exist in naturally immobilized state (as biofilms) with a limited cell division rate and increased stress resilience. In the fields of biotechnology, immobilization of microalgae on artificial cell carriers simplifies biomass harvesting and increases culture robustness and productivity. The choice of a suitable cell carrier is central to biotechnology involving immobilized cultures. Cell carriers based on the natural amine-containing polymer chitosan and synthetic polyethylenimine (PEI) are promising candidates for immobilization of phototrophic microorganisms. This is the first report on the effects of immobilization on PEI and chitosan on the accumulation and composition of polyunsaturated fatty acids, including ARA, in Lobosphaera sp. IPPAS C-2047. Immobilization on PEI increased the ARA percentage in the total fatty acids and ARA accumulation by 72% and 81% compared to the suspended cells cultured in complete or nitrogen-deprived medium 14 days, respectively. Immobilization of Lobosphaera sp. on the chitosan-based carrier reduced the ARA percentage but increased oleic and α-linoleic acid percentages. The mechanisms of the effects of immobilization on the fatty acid profiles of the microalgae are discussed.

Stress buffering after physical activity engagement: An experience sampling study.

While encountering daily hassles is a normative experience, it poses a threat to individuals' daily affective well-being. However, physical activity engagement may help to reduce the current stress-related impact on affective well-being (i.e. stress buffering), which we investigate in this study. Furthermore, we examined the possible moderating role of people's global stress context (i.e. exposure to major life events and chronic stress) on this within-person stress-buffering effect. We approached these ideas using six-times-a-day experience sampling assessments over a period of 22 days. Drawing on a broad national sample of 156 middle-aged adults from the EE-SOEP-IS study, we aimed to elucidate the naturally occurring within-person dynamics of current stress, physical activity engagement, and momentary affect within individuals' everyday lives. Major life events and chronic stress were measured as between-person variables. Multilevel analyses revealed significant within-person associations of current stress and physical activity engagement with momentary affect. Stress-related negative affect was lower when individuals engaged in physical activity, in accordance with the idea of a within-person stress-buffering effect of physical activity engagement. For individuals exposed to more severe major life events, the stress-buffering effect of physical activity engagement for negative affect was lower. Chronic stress did not moderate the within-person stress-buffering effect. Overall, results add to the existing literature that links physical activity to increased stress resilience and emphasizes the need for taking the global between-person stress context into account.

Mindfulness Community Education for High School Students and Guidance and Counseling Teachers

Some events that occur in a adolescence's life can be a source of stress. Stress could cause physical and psychological disorders. Stress resilience allows a person to avoid the negative effects of stress. Objective of this community education activity was to provide initial information about mindfulness as a way of self-empowerment to improve stress resilience of high school students and identify the resilience level to determine the need for further training. The participants in this activity were high school students and guidance-and-counseling teachers. Education about mindfulness were given to high school students and guidance-and-counseling teachers through online meeting platform. Before the education session, participants were asked to voluntarily fill out a Brief Resilience Scale questionnaire to identify the participants' level of stress resilience. At the end of the education, a mindfulness practice session was given. Identification of stress resilience showed that of the 277 participants who filled out the questionnaire, 27.2% had low resilience levels, 72.2% had normal resilience levels, and 0.4% had high resilience levels. The percentage of respondents with low resilience decreased with increasing age (31.5% in adolescents, 22.2% in young adults, and 10.2% in adults). In teacher’s group, 10.71%, 87.50%, and 10.71% of respondents had low, normal, and high resilience, respectively. In student’s group, 68.33% and 31.67% of respondents had normal and high resilience, respectively. A higher percentage of adolescents with low resilience require follow-up. This activity revealed the importance to increase stress resilience which have an impact on improving the learning quality, especially for adolescents as the nation's next generation.

A Resilience Related Glial-Neurovascular Network Is Transcriptionally Activated after Chronic Social Defeat in Male Mice.

Upon chronic stress, a fraction of individuals shows stress resilience, which can prevent long-term mental dysfunction. The underlying molecular mechanisms are complex and have not yet been fully understood. In this study, we performed a data-driven behavioural stratification together with single-cell transcriptomics of the hippocampus in a mouse model of chronic social defeat stress. Our work revealed that in a sub-group exhibiting molecular responses upon chronic stress, the dorsal hippocampus is particularly involved in neuroimmune responses, angiogenesis, myelination, and neurogenesis, thereby enabling brain restoration and homeostasis after chronic stress. Based on these molecular insights, we applied rapamycin after the stress as a proof-of-concept pharmacological intervention and were able to substantially increase stress resilience. Our findings serve as a data resource and can open new avenues for further understanding of molecular processes underlying stress response and for targeted interventions supporting resilience.

Immunization with a heat-killed preparation of Mycobacterium vaccae NCTC 11659 enhances auditory-cued fear extinction in a stress-dependent manner

Stress-related psychiatric disorders including anxiety disorders, mood disorders, and trauma and stressor-related disorders, such as posttraumatic stress disorder (PTSD), affect millions of people world-wide each year. Individuals with stress-related psychiatric disorders have been found to have poor immunoregulation, increased proinflammatory markers, and dysregulation of fear memory. The “Old Friends” hypothesis proposes that a lack of immunoregulatory inputs has led to a higher prevalence of inflammatory disorders and stress-related psychiatric disorders, in which inappropriate inflammation is thought to be a risk factor. Immunization with a soil-derived saprophytic bacterium with anti-inflammatory and immunoregulatory properties, Mycobacterium vaccae NCTC 11659, can lower proinflammatory biomarkers, increase stress resilience, and, when given prior to or after fear conditioning in a rat model of fear-potentiated startle, enhance fear extinction. In this study, we investigated whether immunization with heat-killed M. vaccae NCTC 11659 would enhance fear extinction in contextual or auditory-cued fear conditioning paradigms and whether M. vaccae NCTC 11659 would prevent stress-induced exaggeration of fear expression or stress-induced resistance to extinction learning. Adult male Sprague Dawley rats were immunized with M. vaccae NCTC 11659 (subcutaneous injections once a week for three weeks), and underwent either: Experiment 1) one-trial contextual fear conditioning; Experiment 2) two-trial contextual fear conditioning; Experiment 3) stress-induced enhancement of contextual fear conditioning; Experiment 4) stress-induced enhancement of auditory-cued fear conditioning; or Experiment 5) stress-induced enhancement of auditory-cued fear conditioning exploring short-term memory. Immunizations with M. vaccae NCTC 11659 had no effect on one- or two-trial contextual fear conditioning or contextual fear extinction, with or without exposure to inescapable stress. However, inescapable stress increased resistance to auditory-cued fear extinction. Immunization with M. vaccae NCTC 11659 prevented the stress-induced increase in resistance to auditory-cued fear extinction learning. Finally, in an auditory-cued fear conditioning paradigm exploring short-term memory and fear acquisition, immunization with M. vaccae did not prevent fear acquisition, either with or without exposure to inescapable stress, consistent with the hypothesis that M. vaccae NCTC 11659 has no effect on fear acquisition but enhances fear extinction. These data are consistent with the hypothesis that increased immunoregulation following immunization with M. vaccae NCTC 11659 promotes stress resilience, in particular by preventing stress-induced resistance to fear extinction, and may be a potential therapeutic intervention for trauma- and stressor-related disorders such as PTSD.

The NOP antagonist BTRX-246040 increases stress resilience in mice without affecting adult neurogenesis in the hippocampus

Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of an inhibitory G protein coupled receptor named N/OFQ peptide receptor (NOP). Clinical and preclinical findings suggest that the blockade of the NOP signaling induces antidepressant-like effects. Additionally, the blockade of the NOP receptor during inescapable stress exposure prevented the acquisition of the helplessness phenotype, suggesting that NOP antagonists are able to increase stress resilience. BTRX-246040 (aka LY2940094) is a NOP receptor antagonist with high affinity, potency and selectivity for the NOP over classical opioid receptors. BTRX-246040 is under development for the treatment of depression, eating disorders and alcohol abuse and it already entered clinical trials.In the present study, the antidepressant effects of BTRX-246040 were evaluated in mice subjected to the forced swimming test and to the learned helplessness model of depression. Additionally, the ability of BTRX-246040 to prevent the development of the helpless behavior and to modulate adult hippocampal neurogenesis has been investigated.BTRX-246040 (30 mg/kg, i.p.) produced antidepressant-like effects in the forced swimming test and in the learned helplessness model. More interestingly, when given before the stress induction sessions it was able to prevent the development of the helplessness behavior. Under these experimental conditions, BTRX-246040 did not modulate adult hippocampal neurogenesis, neither in naive nor in stressed mice.This study, performed with a clinically viable ligand, further corroborates growing evidence indicating that the blockade of the NOP signaling may provide an innovative strategy for the treatment of stress related psychopathologies.

Claustrum mediates bidirectional and reversible control of stress-induced anxiety responses.

The processing of stress responses involves brain-wide communication among cortical and subcortical regions; however, the underlying mechanisms remain elusive. Here, we show that the claustrum (CLA) is crucial for the control of stress-induced anxiety-related behaviors. A combined approach using brain activation mapping and machine learning showed that the CLA activation serves as a reliable marker of exposure to acute stressors. In TRAP2 mice, which allow activity-dependent genetic labeling, chemogenetic activation of the CLA neuronal ensemble tagged by acute social defeat stress (DS) elicited anxiety-related behaviors, whereas silencing of the CLA ensemble attenuated DS-induced anxiety-related behaviors. Moreover, the CLA received strong input from DS-activated basolateral amygdala neurons, and its circuit-selective optogenetic photostimulation temporarily elicited anxiety-related behaviors. Last, silencing of the CLA ensemble during stress exposure increased resistance to chronic DS. The CLA thus bidirectionally controls stress-induced emotional responses, and its inactivation can serve as a preventative strategy to increase stress resilience.

Potential of engineering the myo-inositol oxidation pathway to increase stress resilience in plants.

Myo-inositol is one of the most abundant form of inositol. The myo-inositol (MI) serves as substrate to diverse biosynthesis pathways and hence it is conserved across life forms. The biosynthesis of MI is well studied in animals. Beyond biosynthesis pathway, implications of MI pathway and enzymes hold potential implications in plant physiology and crop improvement. Myo-inositol oxygenase (MIOX) enzyme catabolize MI into D-glucuronic acid (D-GlcUA). The MIOX enzyme family is well studied across few plants. More recently, the MI associated pathway's crosstalk with other important biosynthesis and stress responsive pathways in plants has drawn attention. The overall outcome from different plant species studied so far are very suggestive that MI derivatives and associated pathways could open new directions to explore stress responsive novel metabolic networks. There are evidences for upregulation of MI metabolic pathway genes, specially MIOX under different stress condition. We also found MIOX genes getting differentially expressed according to developmental and stress signals in Arabidopsis and wheat. In this review we try to highlight the missing links and put forward a tailored view over myo-inositol oxidation pathway and MIOX proteins.

Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation.

Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FoxO signaling pathway was involved in the regulation of this process. The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte, which was partly mediated by the modulation of the FoxO signaling pathway. These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.

Awareness of maternal stress, consequences for the offspring and the need for early interventions to increase stress resilience.

Experimental and clinical studies suggest that prenatal experiences may influence health trajectories up to adulthood and high age. According to the hypothesis of developmental origins of health and disease exposure of pregnant women to stress, nutritional challenges, infection, violence, or war may "program" risks for diseases in later life. Stress and anxieties can exist or be provoked in parents after fertility treatment, after information or diagnosis of fetal abnormalities and demand simultaneous caring concepts to support the parents. In vulnerable groups, it is therefore important to increase the stress resilience to avoid harmful consequences for the growing child. "Enriched environment" defines a key paradigm to decipher how interactions between genes and environment change the structure and function of the brain. The regulation of the fetal hippocampal neurogenesis and morphology during pregnancy is one example of this complex interaction. Animal experiments have demonstrated that an enriched environment can revert consequences of stress in the offspring during critical periods of brain plasticity. Epigenetic markers of stress or wellbeing during pregnancy might even be diagnosed by fragments of placental DNA in the maternal circulation that show characteristic methylation patterns. The development of fetal senses further illustrates how external stimulation may impact individual preferences. Here, we therefore not only discuss how maternal stress influences cognitive development and resilience, but also design possibilities of non-invasive interventions for both mothers and children summarized and evaluated in the light of their potential to improve the health of future generations.