Mild Stress Research Articles

Impact of Mild Field Drought on the Aroma Profile and Metabolic Pathways of Fresh Tea (Camellia sinensis) Leaves Using HS-GC-IMS and HS-SPME-GC-MS

Aroma plays a pivotal role in defining tea quality and distinctiveness, and tea producers have often observed that specific drought conditions are closely associated with the formation and accumulation of characteristic aroma compounds in tea leaves. However, there is still limited understanding of the differential strategies employed by various tea cultivars in response to drought stress for the accumulation of key volatile aroma compounds in fresh tea leaves, as well as the associated metabolic pathways involved in aroma formation. In this study, two widely cultivated tea cultivars in China, Fuding Dabai (FD) and Wuniuzao (WNZ), were examined to assess the impact of mild field drought stress on the composition and accumulation of key volatile aroma compounds in fresh leaves using headspace gas chromatography–ion mobility spectrometry (HS-GC-IMS) and headspace solid phase micro-extraction gas chromatography–mass spectrometry (HS-SPME-GC-MS) technologies. Results revealed that drought stress led to a substantial increase in the diversity of volatile compounds (VOCs) in FD, while WNZ exhibited a notable rise in low-threshold VOC concentrations, amplifying sweet, floral, fruity, and earthy aroma profiles in post-drought fresh leaves. Through partial least squares discriminant analysis (PLS-DA) of HS-GC-IMS and HS-SPME-GC-MS data, integrating variable importance projection (VIP) scores and odor activity values (OAVs) above 1, 9, and 13, key odor-active compounds were identified as potential markers distinguishing the drought responses in the two cultivars. These compounds serve as crucial indicators of the aromatic profile shifts induced by drought, providing insights into the differential metabolic strategies of the cultivars. Additionally, KEGG enrichment analysis revealed 12 metabolic pathways, such as terpenoid biosynthesis, fatty acid synthesis, cutin, suberine, and wax biosynthesis, and phenylalanine metabolism, which may play crucial roles in the formation and accumulation of VOCs in tea leaves under drought stress. These findings provide a comprehensive framework for understanding the cultivar-specific mechanisms of aroma formation and accumulation in tea leaves under mild drought conditions.

Effects of salt stress on the fruit and yield quality of some selected tomato (<i>Lycopersicum esculentum</i> L.) varieties.

The growth, production, and nutritional characteristics of crops are impacted by abiotic factors such as salinity stress. The study aimed to assess the impact of salt stress on the fruit and yield characteristics of three distinct tomato cultivars, namely Rio, Dan syria, and UTC. Salt solutions with varying concentrations of NaCl were created by dissolving NaCl in deionized water. Four treatments were established, consisting of solutions with salt concentrations of 0g/L (control, without salt), 0.5g/L, 1.0g/L, and 1.5g/L. Each treatment was reproduced three times. The NaCl solutions were administered with a frequency of 7 days. The data in the study underwent Analysis of Variance (ANOVA). Rio outperformed the other varieties in terms of fruit quantity, fresh fruit weight, and fruit pericarp thickness under high salt stress, closely followed by UTC variety. The study also found that Dan syria performed better than the other varieties in terms of fresh and dry weight of shoot, as well as fresh weight of root, under mild and extreme salinity stress. However, Rio performed better than the other varieties in terms of dry weight of root under both mild and extreme salinity stress. The salt tolerance index of the Rio, UTC, and Dan Syria varieties under extreme salinity stress are 46.79%, 20.64%, and 34.70% respectively. This indicated that the Rio variety is the most salt-tolerant of the three types, with Dan Syria variety coming close.

Vitamin C improved anxiety and depression like behavior induced by chronic unpredictable mild stress in adolescent rats by influencing on oxidative stress balance, neurotransmitter systems, and inflammatory response

ABSTRACT Objectives: Stress is an adaptive response to different events in daily life that could strain physically, emotionally, or psychologically. Adolescence is an important developmental period due to physical, psychological, and social maturation. The aim of our study is to state whether chronic unpredictable mild stress (CUMS) during adolescence in male rats can cause anxiety and depression in adulthood and whether vitamin C (Vit C) can prevent this problem or not. Methods: For this purpose, we performed behavioral tests, including open field test, elevated plus maze, and forced swimming test. In addition, we investigated the metabolism of serotonin, the level of inflammation, oxidative stress and brain-derived neurotrophic factor (BDNF) in the brain cortex tissue of animals. Results: Results indicated that CUMS exacerbates mood-related behaviors by affecting the brain oxidative stress balance, inflammatory response, and serotonin metabolism. Moreover, we found that CUMS-Vit C co-treatment could significantly reverse CUMS-induced complications by restoration of the mentioned biochemical parameters. Discussion: Taken together, we would like to suggest the use of Vit C supplementation as a safe, inexpensive, and effective strategy for the management of CUMS.

Effect of acupuncture on AMPK/ULK1 signaling pathway of hippocampus in chronic stress-induced depression rats

To observe the effect of manual acupuncture stimulation on changes of behavior and hippocampal signaling pathways of AMP-activated kinase (AMPK)/UNC-51-like kinase 1 (ULK1) in rats with chronic unpredictable mild stress (CUMS)-induced depression, so as to explore its molecular mechanism underlying improvement of depression. Thirty-two male SD rats were randomly divided into normal control, model, acupuncture and medication (fluoxetine) groups, with 8 rats in each group. The depression model was established by using CUMS (fasting, water depredation, restraint, swimming in cold water, crowding, stroboscope stimulation, and tail clipping, each of which was used once a week) for 6 weeks. Manual acupuncture stimulation was applied to "Baihui"(GV20) and "Yintang"(EX-HN3) for 10 min, once daily, 6 times a week for 6 weeks before every-day modeling. Rats of the medication group received gavage of fluoxetine (10 mg/kg) once a day for 6 weeks before every-day modeling. The percentage of sucrose preference, and the percentages of open arm times and open arm time in the elevated plus maze experiments were detected. The expression levels of AMPK, phosphorylated (p)-AMPK, ULK1, p-ULK1, mammalian target of rapamycin (mTOR) and p-mTOR proteins in the hippocampus tissue were detected by Western blot, and the expression of autophagy effecting protein (Beclin-1) and the selective autophagy receptors (p62) mRNA in the hippocampal tissue was detected using real-time fluorescence quantitative PCR, respectively. Compared with the normal group, the percentage of sucrose preference, percentage of times of entering the open arm and percentage of open arm time, the expression levels of p-AMPK /AMPK ratio, p-ULK1 /ULK1 ratio of proteins, and Beclin-1 mRNA were significantly decreased (P<0.01, P<0.05), and the expression levels of p-mTOR /mTOR ratio and p62 mRNA were significantly increased (P<0.01, P<0.05) in the model group. In comparison with the model group, the percentage of sucrose preference, percentage of open arm times and open arm time, the expression levels of p-AMPK /AMPK ratio, p-ULK1/ULK1 ratio of proteins, and Beclin-1 mRNA were significantly increased in both acupuncture and medication groups (P<0.01, P<0.05), while the expression levels of p-mTOR /mTOR ratio of proteins, and p62 mRNA were markedly decreased only in the medication group (P<0.05). Acupuncture treatment can alleviate depression-like behavior in CUMS rats, which may be related to its functions in up-regulating AMPK/ULK1 signaling pathway to induce cellular autophagy in the hippocampus.

Early monitoring of drought stress in safflower (Carthamus tinctorius L.) using hyperspectral imaging: A comparison of machine learning tools and feature selection approaches

Early detection of drought stress is essential for preventing permanent plant damage and minimizing yield loss. This study utilized hyperspectral imaging at the leaf level to visualize drought stress in safflower plants (Carthamus tinctorius L.). Three safflower genotypes, Palenus, A82, and IL-111, were cultivated under three irrigation levels. Stress conditions were simulated by depleting 50%, 70%, and 90% of soil water content, representing unstressed (US), mild stress (MS), and severe stress (SS) conditions, respectively. Hyperspectral images of leaf samples were captured before any visible signs of water scarcity emerged. Classification analysis was performed using the full mean spectral data with partial least squares discriminant analysis, soft independent modeling of class analogy (SIMCA), support vector machines, and artificial neural network (ANN) classifiers. Feature selection methods were applied to extract the most informative wavebands, and ANN was used to build predictive models. Spatial analysis involved pixel-wise classification using both unsupervised (k-means clustering) and supervised (best classifiers) approaches. ANN outperformed other classifiers using the entire spectral data, effectively distinguishing US, MS, and SS classes in the Palenus, A82, and IL-111 genotypes, achieving F1-scores of 92.22%, 96.01%, and 96.47%, respectively. Among the feature selection methods, SIMCA-based features excelled in monitoring stress conditions in the Palenus and A82 genotypes. In supervised spatial analysis, ANN models clearly depicted the progression of stress in leaves across different genotypes. This study demonstrates the potential of hyperspectral imaging to differentiate various levels of drought stress in safflower, an important oilseed crop.

Effects of Krill Oil and Coconut Oil on Behavioral Changes and Inflammatory Markers in Rats with Chronic Unpredictable Mild Stress Induced Depression Model.

This study was conducted to determine the effects of two different types of fat (krill oil [KO] and coconut oil [CO]) on obesity, behavioral tests, and some inflammatory markers when consumed with a high-fat or control diet in rats with depression. The study was conducted mainly in two phases: the induction of depression (37 days) and the dietary intervention (60 days). After the induction of depression by chronic unpredictable mild stress, dietary intervention started. Sixty male Sprague-Dawley rats were divided into 6 groups with 10 rats in each group: (1) standard diet (SD), (2) SD + 5% KO, (3) SD + 5% medium-chain triglyceride (MCT)* (*CO to contain 5% MCT), (4) high-fat diet (HFD), (5) HFD + 5% KO, and (6) HFD + 5% MCT*. The open field test (OFT), forced swimming test (FST), and sucrose preference test were performed at baseline, end of the depression induction, and dietary intervention to observe behavioral changes in rats. After the final behavioral test, animals were sacrificed, and blood samples were collected for biochemical analyses C-reactive protein (milligram per liter), cortisol (microgram per deciliter), and insulin (micro-international units per milliliter) to assess inflammatory changes in the blood. All data were analyzed under two headings: baseline, end of depression induction, end of dietary intervention, and dietary intervention groups. Body weight gain was highest in the SD+KO and lowest in the SD+MCT group (P < .05). When behavioral tests were evaluated according to dietary intervention, it was found that the SD+MCT group spent the most time in the center, the least time in the periphery, and the lowest immobilization time (P < .05). In FST, the SD+KO with the highest weight gain was the most immobile group (P < .05). The study indicates that the weight-reducing effects of MCTs resulted in positive behavioral responses, particularly in OFT and FST. Through these properties, MCTs can be used medicinally in the prevention and treatment of behavioral changes due to depression.

Hypoxanthine Produces Rapid Antidepressant Effects by Suppressing Inflammation in Serum and Hippocampus.

The occurrence and development of depression are closely related to disorders of the brain and peripheral substances. Abnormal metabolites in the blood affect the signal regulation function of the nerve center, which is one of the key factors for depression episodes. This study was focused on metabolites in serum and the mechanism of its antidepressant in the hippocampus. In the present study, serum metabolites in patients with depression were screened by metabolomic techniques. Various depressive mouse models and behavioral tests were used to assess its antidepressant effects. The expressions of inflammatory signaling were detected by using Western blot, ELISA, and immunofluorescence. We found that the metabolite hypoxanthine in the serum of patients with depression was significantly reduced, and the same result was also found in two mouse models of depression such as chronic unpredictable mild stress (CUMS) and social defeat stress (SD). By administering different doses of hypoxanthine (5, 10, 15 mg/kg), we found that only 15 mg/kg was able to significantly reduce the latency and increase food consumption in the novelty suppressed-feeding test (NSF), which was also able to reverse the depressive phenotypes of mice in the CUMS model after a single administration at 2 h later. Hypoxanthine obviously reduced the expressions of inflammation in serum and downregulated the expressions of MAPK and NLRP3-related pathways in the hippocampus in CUMS mice. Moreover, hypoxanthine also suppressed the activations of glial cells including GFAP and IBA-1 in hippocampal CA1, CA3, and dentate gyrus (DG). To sum up, hypoxanthine exerted antidepressant effect relying on the inhibition of peripheral and hippocampal inflammations by regulating MAPK, NLRP3-related pathways, and glial cells. This was the first time that we have found a disordered metabolite in patients with depression and further systematically demonstrated its efficacy and potential mechanism of antidepressants, providing new ideas for antidepressant drug development.

GABAB modulate NF-κB/NLRP3 pathways in electroacupuncture prevention of depression in CUMS rats

BackgroundOur previous research has demonstrated that electroacupuncture (EA) has the potential to mitigate depression-like symptoms resulting from chronic stress. However, further investigation is required to fully understand the underlying mechanisms. The regulatory role of γ-aminobutyric acid type B (GABAB) in synaptic plasticity and the involvement of NF-κB/NLRP3-mediated inflammation in the lateral habenula nucleus (LHb) are key factors in the development of depression. This study sought to investigate the potential of EA in mitigating depression-like symptoms induced by chronic stress through mechanisms such as enhancing GABAB levels, regulating synaptic plasticity in the LHb, and suppressing NF-κB/NLRP3-mediated inflammation. MethodsSprague-Dawley rats were exposed to chronic unpredictable mild stress (CUMS) in order to create a model of depression. Subsequently, the weight and behavioral assessments of all rats were monitored, and samples of the lateral habenula and serum were collected. The protein expression levels were analyzed using western blotting. The 5-hydroxytryptophan (5-HT), Dopamine (DA), and Norepinephrine (NE) in the LHb and serum were measured using ELISA. The alterations in GABAB and NF-κB in the LHb were observed through immunofluorescence. The neuronal damage in the LHb was assessed using Nissl staining. ResultsEA upregulated the expression of GABAB in the LHb of rats subjected to CUMS. Subsequent behavioral assessments indicated that blocking GABAB attenuated the antidepressant effects of EA in CUMS-exposed rats. Furthermore, EA enhanced synaptic plasticity in the LHb of CUMS-exposed rats and mitigated NF-κB/NLRP3-mediated inflammatory responses, with these effects potentially being reversed by GABAB inhibition. ConclusionThrough the promotion of GABAB levels, regulation of synaptic plasticity within the LHb, and inhibition of NF-κB/NLRP3-mediated neuroinflammation in the same region, electroacupuncture at Shangxing and Fengfu acupoints demonstrates efficacy in mitigating depression-like behaviors induced by CUMS.

The Divergent Responses of Salinity Generalists to Hyposaline Stress Provide Insights Into the Colonisation of Freshwaters by Diatoms.

Environmental transitions, such as the salinity divide separating marine and fresh waters, shape biodiversity over both shallow and deep timescales, opening up new niches and creating opportunities for accelerated speciation and adaptive radiation. Understanding the genetics of environmental adaptation is central to understanding how organisms colonise and subsequently diversify in new habitats. We used time-resolved transcriptomics to contrast the hyposalinity stress responses of two diatoms. Skeletonema marinoi has deep marine ancestry but has recently invaded brackish waters. Cyclotella cryptica has deep freshwater ancestry and can withstand a much broader salinity range. Skeletonema marinoi is less adept at mitigating even mild salinity stress compared to Cyclotella cryptica, which has distinct mechanisms for rapid mitigation of hyposaline stress and long-term growth in low salinity. We show that the cellular mechanisms underlying low salinity tolerance, which has allowed diversification across freshwater habitats worldwide, includes elements that are both conserved and variable across the diatom lineage. The balance between ancestral and lineage-specific environmental responses in phytoplankton have shaped marine-freshwater transitions on evolutionary timescales and, on contemporary timescales, will affect which lineages survive and adapt to changing ocean conditions.

Exosomes Derived from DPA-treated UCMSCs Attenuated Depression-like Behaviors and Neuroinflammation in a Model of Depression Induced by Chronic Stress.

Depression is characterized by both neuroinflammation and neurodegeneration. Exosomes (Exo) have been shown to function as inhibitors of inflammation and promoters of neurogenesis. Omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid, can combat depression by increasing levels of docosapentaenoic acid (DPA). This study explored the effects of DPA on the therapeutic potential of Exo derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in glia-induced neuroinflammation associated with depression. Exposure to chronic unpredictable mild stress (CUMS) over six weeks induced depression- and anxiety-like behaviors, while decreasing the levels of serotonin and dopamine. Molecularly, CUMS increased the concentrations of the microglial M1 markers Iba1, iNOS, and IL-1β, while reducing the M2 markers Arg1, CD206, and IL-10 in the prefrontal cortex and hippocampus. However, Exo therapy reversed these effects. Moreover, DPA treatment of Exo demonstrated superior efficacy in alleviating depressive behaviors, neurotransmitter deficiencies, and M1 microglial activation. In vitro, Exo suppressed LPS-stimulated BV2 cell viability and M1 microglial activation, while mitigating the SH-SY5Y cell apoptosis triggered by treatment with the conditioned medium from LPS-activated BV2 cells. Furthermore, administration of DPA enhanced this effect. Mechanically, DPA enhanced Exo function by upregulating miR125b-5p expression, thereby targeting the MyD88/TRAF6/NF-κB signaling pathway. In summary, Exo exhibited antidepressant effects by suppressing M1 microglial neuroinflammation, while DPA treatment provided a more potent therapeutic effect on depression-like changes through the upregulation of miR125b-5p targeting the MyD88/TRAF6/NF-κB pathway.

Asiaticoside improves depressive-like behavior in mice with chronic unpredictable mild stress through modulation of the gut microbiota.

Asiaticoside, the main active ingredient of Centella asiatica, is a pentacyclic triterpenoid compound. Previous studies have suggested that asiaticoside possesses neuroprotective and anti-depressive properties, however, the mechanism of its anti-depressant action not fully understood. In recent years, a growing body of research on anti-depressants has focused on the microbiota-gut-brain axis, we noted that disruption of the gut microbial community structure and diversity can induce or exacerbate depression, which plays a key role in the regulation of depression. Behavioral experiments were conducted to detect depression-like behavior in mice through sucrose preference, forced swimming, and open field tests. Additionally, gut microbial composition and short-chain fatty acid (SCFA) levels in mouse feces were analyzed 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Hippocampal brain-derived neurotrophic factor (BDNF) and 5-hydroxytryptamine receptor 1A (5-HT1A) expression in mice was assessed by western blotting. Changes in serum levels of inflammatory factors, neurotransmitters, and hormones were measured in mice using ELISA. This study revealed that oral administration of asiaticoside significantly improved depression-like behavior in chronic unpredictable mild stress (CUMS) mice. It partially restored the gut microbial community structure in CUMS mice, altered SCFA metabolism, regulated the hypothalamic-pituitary-adrenal axis (HPA axis) and inflammatory factor levels, upregulated BDNF and 5-HT1A receptor protein expression, and increased serum serotonin (5-hydroxytryptamine, 5-HT) concentration. These findings reveal that asiaticoside exerts antidepressant effects via the microbiota-gut-brain axis. These results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model.

Stress Levels and Coping Strategies in Medical Students and its Association with Salivary IL-6 Levels

Background: Medical students face ongoing stress during their training but have developed coping mechanisms. Stress alters various physiological processes, including pro-inflammatory markers like Interleukin-6(IL-6). The present study was conducted to assess stress levels and coping strategies in medical students and their association with salivary IL-6 levels. Methods: This descriptive study was conducted after obtaining institutional ethical clearance. A total of 76 consenting undergraduate medical students answered the Cohen’s perceived stress scale and BriefCOPE questionnaire. Unstimulated saliva was used to assess salivary IL-6 levels using a Diaclone human IL-6 ELISA kit and the data obtained was analyzed. Results: Out of the 76 participants, 59(77.6%) were female and 17(22.4%) were male. Mild stress was reported by 9 students, moderate by 53, and severe stress by 14 students. Based on Kruskal-Wallis p test, most students used approach coping for stress of all levels. This active strategy involves problem-solving and future planning. Approach coping has shown better responses to adversity, physical health, and emotional responsiveness. Mild and moderate stressed students used acceptance, positive-refrain, and planning, while severe stressed students used planning, self-distraction, and self-blame. Despite the perceived stress, there were no significant differences in the salivary IL-6 levels among the three categories. Conclusion: ‘Approach’ coping was commonly used and linked to positive outcomes. Despite this, a number of students have reported to experience stress. Therefore, more effective strategies are needed to handle stress and demands of the profession effectively. Further research with larger samples is recommended to explore salivary IL-6 levels’ relation to stress.

Negative Emotions and e-Learning Academic Performance of Engineering Students in a Private University

One of the early pandemic COVID-19 effects on the educational sector is that learning activities needto be conducted fully online (e-learning). This circumstance can trigger negative emotions thatcontribute to students’ academic performance. This study aimed to find empirical data regarding therelationship of negative emotions and students academic performance in this particular situation. Thestudy was a cross-sectional quantitative method. Questionnaire of negative emotion (DASS-21)Indonesian version was deployed using google form to students of Industrial Engineering andInformation Systems class of 2020 using convenience sampling. 292 questionnaires were returnedand used. Findings: All three negative emotions (depression, anxiety, and stress) were experiencedby students at different levels. Negative emotions had different correlations to academic performance.There were no significant differences between anxiety and depression to students’ academicperformance (anxiety: F (3) = 2.202, ρ = 0.088, depression: F (2) = 1.397, ρ = 0.249). Two-wayANOVA showed that students who experienced mild stress performed better than those with normalstress category (F (1) = 3.933, ρ = 0.048). Female students significantly had better academicperformance compared to male students (ρ (0.001) &lt; α= 0.05)) and that students experienced mildstress, performed better than those with normal stress category. Managing stress at a moderate levelis beneficial and can be done by media or counseling or other catharsis methods. Further study usinglarger samples from non engineering majors and randomized sampling is needed for generalizationas well as identifying factors that contribute to e-learning performance in a special situation.

Infralimbic Cortex and Behavioral Responses to Mild Stress after Repeated Social Stress Exposure

Major Depressive Disorder (MDD) is an emotional impairment that can have debilitating consequences for afflicted individuals. Social stress, including isolation or alienation, may be an important factor that contributes to MDD. In two experiments, repeated social defeat was utilized in rodents to induce social stress, modeling the social stressors that are thought to contribute to MDD in humans. Behavioral analyses revealed that dominance and submissive behaviors in the social defeat sessions were quite stable across repeated sessions. Accordingly, there appeared to be little variability between the rats in their social stress experience. This validates the model and allows for the study to draw inferences concerning the impacts of the stress experience from means testing of behavioral and physiological outcomes. The second experiment evaluated the impacts of repeated social defeat on cortical responses to the mild stress of a novel environment. RNAscope was utilized evaluate expression of c-Fos, GAD65, and VGluT1 mRNA in the infralimbic cortex. mRNA for c-Fos was labeled to identify which neurons were active in the infralimbic cortex. This was combined with labels for vGluT1 and GAD65 mRNAs to evaluate if those neurons were excitatory (glutamatergic) or inhibitory (GABAergic). The socially stressed rats exhibited increased mRNA expression for GAD65 in the infralimbic cortex. This suggests increased stress-induced biosynthesis of GABA in inhibitory neurons of the infralimbic cortex.

Chronic stress in adulthood results in microvascular dysfunction and subsequent depressive-like behavior

Depression is a prevalent mental disorder characterized by unknown pathogenesis and challenging treatment. Recent meta-analyses reveal an association between cardiovascular risk factors and an elevated risk of depression. Despite this, the precise role of vascular injury in depression development remains unclear. In this investigation, we assess vascular system function in three established animal models of depression— chronic unpredictable mild stress (CUMS), chronic social defeat stress (CSDS) and maternal separation (MS)—utilizing ultrasonography and laser Doppler measurement. All three model animals exhibit anhedonia and despair-like behavior. However, significant microvascular dysfunction (not macrovascular) is observed in animals subjected to CUMS and CSDS models, while such dysfunction is absent in the MS model. Statistical analysis further indicates that microcirculation dysfunction is not only associated with depression-like behavior but is also intricately involved in the development of depression in the CUMS and CSDS models. Furthermore, our study has proved for the first time that endothelial nitric oxide synthase-deficient (eNOS+/−) mice, which is a classic model of vascular endothelial injury, showed depression-like behavior which occurred two months later than microvascular dysfunction. Notably, the mitigation of microvascular dysfunction successfully reverses depression-like behavior in eNOS+/− mice by enhancing nitric oxide production. In conclusion, this study unveils the pivotal role of microvascular dysfunction in the onset of depression induced by chronic stress in adulthood and proposes that modulating microvascular function may serve as a potential intervention in the treatment of depression.

Breakdown of the blood-brain barrier in depressed mice induced by chronic unpredictable mild stress

BackgroundRecent studies have suggested potential impairment of the blood-brain barrier (BBB) in depression. However, due to the limited research and variability in animal models, further investigation using diverse and stable models is necessary. MethodsA male mouse model of depression was established using the chronic unpredictable mild stress (CUMS) protocol. Following model establishment, depression-like behaviors were assessed using the sucrose preference test, tail suspension test, and forced swimming test. Morphological changes in the hippocampus were examined through hematoxylin-eosin staining. BBB permeability was evaluated using the Evans blue leakage test, fluorescein sodium (NaF) leakage test, and serum S100B content assessment. Gene and protein expression levels of BBB-related proteins in the hippocampus were determined via real-time PCR, western blotting, and immunofluorescence assays. ResultsCUMS exposure induced depression-like behaviors, including reduced body weight gain, diminished sucrose preference, and prolonged immobility in both the tail suspension test and forced swimming test. While no significant pathological changes were observed in the hippocampus of either group, increased BBB permeability was noted in the CUMS group, as evidenced by enhanced NaF leakage into the brain parenchyma and elevated serum S100B levels. Gene expression analysis revealed downregulation of angiogenesis-related genes and tight junction proteins in the CUMS group. Additionally, protein levels of tight junction proteins Claudin-5 and ZO-1 were lower in the CUMS group compared to controls. LimitationsThis study is limited to a male mouse model, and the BBB in females is worth exploring in the future. ConclusionsIncreased BBB permeability and decreased expression of tight junction proteins Claudin5 and ZO-1 were observed in mice with CUMS-induced depression.

Lacticaseibacillus paracasei 207-27 alters the microbiota-gut-brain axis to improve wearable device-measured sleep duration in healthy adults: a randomized, double-blind, placebo-controlled trial.

Objective: Probiotics have been reported to exert beneficial effects on sleep through the gut-brain axis. Therefore, this randomized, double-blind, placebo-controlled trial assessed the effects of Lacticaseibacillus paracasei 207-27 supplementation on sleep quality and its safety and potential mechanisms. Method and study design: Healthy adults under mild stress aged 18-35 years consumed low or high doses of L. paracasei 207-27 or a placebo for 28 days. Fecal samples, blood samples, and questionnaires were collected at the baseline and the end of the intervention. Sleep quality was measured using wearable devices and Pittsburgh sleep quality index (PSQI) questionnaire. Serum inflammatory markers, corticotropin-releasing hormone, adrenocorticotropic hormone (ACTH), cortisol (COR), γ-aminobutyric acid, and 5-hydroxytryptamine levels were detected using enzyme-linked immunosorbent assay. The gut microbiota was analyzed using 16S rRNA sequencing and bioinformatics. Short-chain fatty acids levels were detected using gas chromatography-mass spectrometry. Results: Both the low-dose and high-dose groups exhibited significant improvements in wearable device- measured sleep duration compared to the placebo group. The global scores of PSQI in three groups significantly decreased after intervention without statistical difference between groups. At the phylum level, the low-dose group exhibited a higher relative abundance of Bacteroidota and a lower Firmicutes-to-Bacteroidetes (F/B) ratio. At the genus level, two treatment groups had higher relative abundance of Bacteroides and Megamonas, alongside lower levels of Escherichia-Shigella. Furthermore, the low-dose group exhibited significant increases in acetic acid, propionic acid, butyric acid, and valeric acid levels, while two treatment groups exhibited a significant decrease in COR levels. Correlation analysis revealed that the increased levels of acetic acid and butyric acid in the low-dose group may be associated with decreased ACTH. Conclusion: L. paracasei 207-27 administration in healthy adults resulted in improvements in gut microbiota community and sleep duration. The mechanisms might involve modulation of the gut microbiota structure to regulate the function of the gut-brain axis, including increases in SCFA levels and decreases in hypothalamic-pituitary-adrenal axis activity. The Chinese clinical trial registry number is ChiCTR2300069453 (https://www.chictr.org.cn/showproj.html?proj=191193, registered 16 May 2023 - retrospectively registered).

Stress-mediated Activation of Ferroptosis, Pyroptosis, and Apoptosis Following Mild Traumatic Brain Injury Exacerbates Neurological Dysfunctions.

Nearly half of mild traumatic brain injury (mTBI) patients continue to experience residual neurological dysfunction, which may be attributed to exposure to stress. Ferroptosis, a newly discovered form of cell death, is increasingly recognized for its involvement in the pathophysiology of TBI. Understanding the mechanisms by which stress influences mTBI, particularly through ferroptosis, is crucial for the effective treatment and prevention of mTBI patients who are sensitive to stressful events. In our study, a mouse mTBI model was established. An acute restraint stress (RS) and a chronic unpredictable mild stress (CUMS) model then were applied to make acute and chronic stress, respectively. We found acute RS significantly delayed the recovery of reduced body weight and short-term motor dysfunctions and exacerbated cell insults and blood-brain barrier leakage caused by mTBI. Further studies revealed that acute RS exacerbates neuronal ferroptosis, pyroptosis, and apoptosis by promoting iron overloading in the neocortex following mTBI. Interestingly, the inhibition of ferroptosis with iron chelators, including deferoxamine and ciclopirox, reversed pyroptosis and apoptosis. Moreover, CUMS aggravated neurological dysfunctions (motor function, cognitive function, and anxiety-like behavior) and exacerbated brain lesion volume. CUMS also exacerbates ferroptosis, pyroptosis, and apoptosis by intensifying iron deposition, along with decreasing the expression of neuronal brain-derived neurotrophic factor and glucocorticoid receptor in the neocortex post mTBI. These effects were also mitigated by iron chelators. Our findings suggest that alleviating ferroptosis induced by iron deposition may represent a promising therapeutic approach for mTBI patients who have experienced stressful events.

Role of vitamin E on bovine skeletal-muscle-derived cells from Korean native cattle under heat treatment.

Our study aimed to evaluate the dualistic effect of heat stress on muscle differentiation at different temperatures, and whether vitamin E, a powerful antioxidant, could offset any negative effects, using bovine skeletal-muscle-derived cells (BSMCs) with myogenic properties. The BSMCs were extracted from the skeletal muscle of thirty-month-old Korean native cattle and subjected to myogenic differentiation under three heat exposure conditions: 37°C (control; CON), 39°C (mild heat stress; MHS), and 41°C (severe heat stress; SHS) for 24h with or without vitamin E treatment (NE or VE). After 24h treatments, the cells were returned to 37°C incubators and differentiated until day 6. On day 1, because of the heat exposure, the gene expression of MYOG was the highest in MHS (P = 0.047), suggesting a promotive effect of mild heat stress on myogenic differentiation, while on day 6, compared to CON and MHS, MYOD (P = 0.013) and MYOG (P = 0.029) were the lowest in SHS. Vitamin E treatment also lowered MYOG (P = 0.097), regardless of heat exposure. On day 1, HSPB1 (P = 0.001) and HSP70 (P < 0.001) were the highest in SHS, and an interaction between heat exposure and vitamin E treatment was found on day 6 (P < 0.027). BCL-2 was also the highest on day 1 in SHS (P = 0.05), and an interaction of heat exposure and vitamin E treatment was found on day 1 on BAX expression (P = 0.038). For antioxidant genes, SOD1 (P = 0.002) and GPX1 (P < 0.001) were affected by heat exposure, with the highest levels being observed in SHS, and on day 6, GPX1 was still the highest in SHS (P = 0.027). The fusion index was also affected by heat exposure, showing a decrease in SHS and an increase in MHS compared to CON (P < 0.001). Significant effects were noted from heat exposure (P < 0.001), vitamin E treatment (P < 0.001), and the interaction of heat exposure and vitamin E treatment (P = 0.002) on the protein content. Taken together, our findings provide evidence that vitamin E could ameliorate the harmful effects of heat exposure by modulating heat shock proteins and apoptosis regulators, improving the protein synthesis of BSMCs during myogenic differentiation. These results suggest that vitamin E supplementation could potentially protect muscle development in beef cattle under summer heat stress.

Chronic treatment with the antipsychotic lurasidone modulates the neuroinflammatory changes associated with the vulnerability to chronic mild stress exposure in female rats

Stress exposure is a key risk factor for the developmentof depressive-like conditions. However, despite the higher incidence of Major Depressive Disorder in the female population, classical stress-based experimental paradigms have primarily focused on males. In the present study, we used the well-established chronic mild stress (CMS) paradigm to investigate the development of anhedonia, a cardinal symptom of affective disorders, in the female animals and we also studied the potential effect of the antipsychotic drug lurasidone in normalizing the alterations brought about by stress exposure. We found that three weeks of CMS exposure produced a significant reduction of sucrose intake in 50% of the animals (vulnerable, CMS-V), whereas the others were resilient (CMS-R). The development of an anhedonic phenotype in CMS-V was associated with a significant elevation of different immune markers, such as Complement C3 and C4, and inflammatory cytokines, including INFß and Il1ß in dorsal and ventral hippocampus. Interestingly, sub-chronic treatment with the antipsychotic drug lurasidone was able to revert the anhedonic phenotype while normalizing most of the molecular alterations found in rats vulnerable to CMS exposure. This study extends the ability of lurasidone to normalize the anhedonic phenotype in CMS rats also to females. Moreover, we provide novel evidence on lurasidone’s potential effectiveness in treating mental disorders characterized by immune-inflammatory dysfunction.