Search Results (652)

Maternal immune activation (MIA) during pregnancy has been increasingly recognized as a critical factor in the development of neurodevelopmental disorders, with potential sex-specific impacts that are not yet fully understood. In this study, we utilized a murine model to explore the behavioral and molecular consequences of MIA induced by lipopolysaccharide (LPS) administration on embryonic day 12.5. Our findings indicate that male offspring exposed to LPS exhibited significant increases in anxiety-like and depression-like behaviors, while female offspring did not show comparable changes. Molecular analyses revealed alterations in pro-inflammatory cytokine levels and synaptic gene expression in male offspring, suggesting that these molecular disruptions may underlie the observed behavioral differences. These results emphasize the importance of considering sex as a biological variable in studies of neurodevelopmental disorders and highlight the need for further molecular investigations to understand the mechanisms driving these sex-specific outcomes. Our study contributes to the growing evidence that prenatal immune challenges play a pivotal role in the etiology of neurodevelopmental disorders and underscores the potential for sex-specific preventative approaches of MIA. Full article

Mental health disparities exist between rural and metro areas of the United States. Differences in dietary intake may contribute to these disparities. We examined differences in dietary intake and mental health between those 50 years and older (n = 637) living in rural counties to those living in metro counties in North Dakota and the relationship between dietary intake to days with depression or anxiety. A survey was conducted throughout North Dakota. Items were modified from other surveys, such as the Behavioral Risk Factor Surveillance System questionnaires and the National Health Interview Survey Cancer Control Supplement Dietary Screener Questionnaire. Comparing medians, individuals more likely to be unable to perform normal daily activities due to mental health (p = 0.009) resided in rural areas instead of metro areas. Those living rurally also ate more processed meats (p = 0.005), while trending toward less lean protein intake (p = 0.056). Multinomial regression analyses controlling for covariates revealed that lean protein intake and fruit intake were inversely associated with days with depression and anxiety (all p < 0.05), whereas processed meat intake was positively associated with anxiety (p = 0.005). Clinicians working with older adults residing in rural areas should emphasize substituting lean proteins for processed meats. Full article

We investigated associations between polysubstance use and behavioral problems among adolescents. Because substance use becomes more developmentally normative with age, we examined whether polysubstance use was less likely to co-occur with behavioral problems among older (vs. younger) adolescents. Using data from a nationally representative survey of US high school students, we compared the association between polysubstance use (i.e., use of alcohol, cannabis, tobacco/nicotine, and illicit drugs) and behavioral problems (i.e., suicide attempts, depressive symptoms, poor school performance, and sexual risk behaviors) by grade level. We conducted latent class analysis (LCA) to characterize patterns of polysubstance use, and multi-group LCA to estimate invariance by grade. Among the three latent classes that emerged, classes were distinguished by having low, moderate, and high probabilities for behavior problems and use of substances. Class I comprised 52% of the sample, whereas classes II and III comprised 35% and 12% of the sample, respectively. The multi-group LCA showed that younger adolescents had a higher relative probability of co-occurring problem behaviors and polysubstance use. Findings may be helpful in targeting screening and prevention efforts of high school students by grade. Specifically, our results provide evidence that associations between behavioral problems and alcohol/drug use are weaker in later high school grades, suggesting that substance use may not be a weaker marker of behavioral problems for students in higher grades. Full article

Post-stroke depression (PSD) represents a significant neuropsychiatric complication that affects between 39% and 52% of stroke survivors, leading to impaired recovery, decreased quality of life, and increased mortality. This comprehensive review synthesizes our current knowledge of PSD, encompassing its epidemiology, risk factors, underlying neurochemical mechanisms, and the existing tools for preclinical investigation, including animal models and behavioral analyses. Despite the high prevalence and severe impact of PSD, challenges persist in accurately modeling its complex symptomatology in preclinical settings, underscoring the need for robust and valid animal models to better understand and treat PSD. This review also highlights the multidimensional nature of PSD, where both biological and psychosocial factors interplay to influence its onset and course. Further, we examine the efficacy and limitations of the current animal models in mimicking the human PSD condition, along with behavioral tests used to evaluate depressive-like behaviors in rodents. This review also sets a new precedent by integrating the latest findings across multidisciplinary studies, thereby offering a unique and comprehensive perspective of existing knowledge. Finally, the development of more sophisticated models that closely replicate the clinical features of PSD is crucial in order to advance translational research and facilitate the discovery of future effective therapies. Full article

Obstructive Sleep Apnea (OSA) is a disorder characterized by repeated upper airway collapse during sleep, leading to apneas and/or hypopneas, with associated symptoms like intermittent hypoxia and sleep fragmentation. One of the agents contributing to OSA occurrence and development seems to be serotonin (5-HT). Currently, the research focuses on establishing and interlinking OSA pathogenesis and the severity of the disease on the molecular neurotransmitter omnipresent in the human body—serotonin, its pathway, products, receptors, drugs affecting the levels of serotonin, or genetic predisposition. The 5-HT system is associated with numerous physiological processes such as digestion, circulation, sleep, respiration, and muscle tone—all of which are considered factors promoting and influencing the course of OSA because of correlations with comorbid conditions. Comorbidities include obesity, physiological and behavioral disorders as well as cardiovascular diseases. Additionally, both serotonin imbalance and OSA are connected with psychiatric comorbidities, such as depression, anxiety, or cognitive dysfunction. Pharmacological agents that target 5-HT receptors have shown varying degrees of efficacy in reducing the Apnea-Hypopnea Index and improving OSA symptoms. The potential role of the 5-HT signaling pathway in modulating OSA provides a promising avenue for new therapeutic interventions that could accompany the primary treatment of OSA—continuous positive airway pressure. Thus, this review aims to elucidate the complex role of 5-HT and its regulatory mechanisms in OSA pathophysiology, evaluating its potential as a therapeutic target. We also summarize the relationship between 5-HT signaling and various physiological functions, as well as its correlations with comorbid conditions. Full article

(1) Background: During and after the pandemic, individuals with type 1 and type 2 diabetes struggled to maintain a healthy lifestyle due to psychological distress and the struggle to accommodate contextual challenges and changes in their family and work obligations and expectations. This study aims to explore the long-term impacts of the pandemic on proactive self-management behaviors and outcomes that consider contextual and environmental factors, such as family and work dynamics. (2) Methods: In this mixed-method study, data were collected from 418 participants using the Hospital Anxiety and Depression Scale (HADS) and the Insomnia Severity Index (ISI), followed by 16 individual interviews. (3) Results: The prevalence of depression was 37.1%, that of anxiety was 59.1%, and that of insomnia was 66.3%. Significant differences were observed in anxiety by age (p = 0.02), while individuals with other comorbidities were more likely to report insomnia (p = 0.3). Overall, various challenges during the pandemic have exacerbated emotional distress and complicated self-care routines and adherence to healthy lifestyles. (5) Conclusions: The COVID-19 pandemic has prompted individuals with type 1 and 2 diabetes to adopt alternative health-management methods, such as self-care, proactive initiatives, and daily challenges. Enhancing proactiveness, awareness, and an understanding of individuals’ needs is crucial for alleviating stress, controlling disease, and preparing for potential future health crises in the wake of the pandemic’s long-term effects. Full article

The literature shows that maternal stress can influence behavior and immune function in F1. Yet, most studies on these are from the laboratory, and replicated studies on the mechanisms by which maternal stress drives individual characteristics are still not fully understood in wild animals. We manipulated high- and low-density parental population density using large-scale field enclosures and examined behavior and immune traits. Within the field enclosures, we assessed anti-keyhole limpet hemocyanin immunoglobulin G (anti-KLH IgG) level, phytohemagglutinin (PHA) responses, hematology, cytokines, the depressive and anxiety-like behaviors and prevalence and intensity of coccidial infection. We then collected brain tissue from juvenile voles born at high or low density, quantified mRNA and protein expression of corticotropin-releasing hormone (CRH) and glucocorticoid receptor gene (NR3C1) and measured DNA methylation at CpG sites in a region that was highly conserved with the prairie vole CRH and NR3C1 promoter. At high density, we found that the F1 had a lower DNA methylation level of CRH and a higher DNA methylation level of NR3C1, which resulted in an increase in the expression levels of the CRH mRNA and protein expression and further reduced the expression levels of the NR3C1 mRNA and protein expression, and ultimately led to have delayed responses to acute immobilization stress. Juvenile voles born at high density also reduced anti-KLH IgG levels and PHA responses, increased cytokines, and depressive and anxiety-like behaviors, and the effects further led to higher coccidial infection. From the perspective of population density inducing the changes in behavior and immunity at the brain level, our results showed a physiological epigenetic mechanism for population self-regulation in voles. Our results indicate that altering the prenatal intrinsic stress environment can fundamentally impact behavior and immunity by DNA methylation of HPA-axis genes and can further drive population fluctuations in wild animals. Full article

Recently, research has confirmed that jasmine tea may help improve the depressive symptoms that are associated with psychiatric disorders. Our team previously found that jasmine tea improved the depressive-like behavior that is induced by chronic unpredictable mild stress (CUMS) in Sprague Dawley (SD) rats. We hypothesized that the metabolic disorder component of depression may be related to the gut microbiota, which may be reflected in the metabolome in plasma. The influence of jasmine tea on gut microbiota composition and the association with depressive-related indexes were explored. Furthermore, the metabolites in plasma that are related to the gut microbiota were identified. SD rats were treated with control or CUMS and administrated jasmine tea for 8 weeks. The 16S rRNA gene amplicon sequencing was used to analyze the gut microbiota in feces samples, and untargeted metabolomics was used to analyze the metabolites in plasma. The results found that jasmine tea significantly ameliorated the depressive behavior induced by CUMS, significantly improved the neurotransmitter concentration (BDNF and 5-HT), and decreased the pro-inflammation levels (TNF-α and NF-κB). The intervention of jasmine tea also alleviated the dysbiosis caused by CUMS; increased the relative abundance of Bacteroides, Blautia, Clostridium, and Lactobacillus; and decreased Ruminococcus and Butyrivibrio in the CUMS-treated rats. Furthermore, the serum metabolites of the CUMS-treated rats were reversed after the jasmine tea intervention, i.e., 22 were up-regulated and 18 were down-regulated, which may have a close relationship with glycerophospholipid metabolism pathways, glycine serine and threonine metabolism pathways, and nicotinate and nicotinamide metabolism pathways. Finally, there were 30 genera of gut microbiota related to the depressive-related indexes, and 30 metabolites in the plasma had a strong predictive ability for depressive behavior. Potentially, our research implies that the intervention of jasmine tea can ameliorate the depression induced by CUMS via controlling the gut flora and the host’s metabolism, which is an innovative approach for the prevention and management of depression. Full article

Microglia respond to stressors by secreting cytokines or growth factors, playing a crucial role in maintaining brain homeostasis. While the antidepressant-like effects of Polygonatum sibiricum polysaccharides (PSPs) have been observed in mice, their potential effectiveness involving microglial regulation remains unknown. This study investigates the antidepressant-like mechanism of PSP by regulating microglial phenotype and signaling pathways in the prefrontal cortex of chronic restraint stress (CRS)-induced mice. PSP was extracted, purified, characterized, and orally administered to CRS mice. High-performance gel permeation chromatography (HPGPC) revealed that PSP has a molecular weight of 5.6 kDa. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that PSP exhibited a layered structure with densely packed, irregular surfaces. PSP treatment significantly increased sucrose preference (low: 71%, p < 0.01; medium: 69%, p < 0.05; high: 75%, p < 0.001 vs. CRS: 58%) and reduced immobility time (low: 74 s, p < 0.01; medium: 68 s, p < 0.01; high: 79 s, p < 0.05 vs. CRS: 129 s), indicating the alleviation of depressive-like behaviors. PSP inhibited microglial activation (PSP, 131/mm² vs. CRS, 173/mm², p = 0.057), reversing CRS-induced microglial hypertrophy and hyper-ramification. Furthermore, PSP inactivated microglial activation by inhibiting NLRP3/ASC/caspase-1/IL-1β signaling pathways, increasing BDNF synthesis and activating brain-derived neurotrophic factor (BDNF)-mediated neurogenesis (PSP, 80/per DG vs. CRS, 49/per DG, p < 0.01). In conclusion, PSP exerts antidepressant-like effects through the regulation of microglial activity and neuroinflammatory pathways, indicating it as a potential natural compound for depression treatment. Full article

The pharmacological effects of pomegranates have been described considering metabolic aspects such as hypoglycemic and hypolipidemic activities. The pomegranate extract has activity on the central nervous system (CNS) as a natural antidepressant and anxiolytic. The chemical composition of pomegranates is complex since the bioactive compounds are multiple secondary metabolites that have been identified in the extracts derived from the peel, seed, flowers, leaves, or in their combination; so, it has not been easy to identify an individual compound as responsible for its observed pharmacological properties. From this point of view, the present review analyzes the effects of crude extracts or fractions of pomegranates and their possible mechanisms of action concerning antidepressant- and anxiolytic-like effects in animal models. Serotonin receptors, estrogen receptors, the peroxisome proliferator-activated receptor gamma (PPARγ), or monoamine oxidase enzymes, as well as potent antioxidant and neuroplasticity properties, have been described as possible mediators involved in the antidepressant- and anxiolytic-like behaviors after pomegranate treatment. The pharmacological effects observed on the CNS in experimental models associated with a specific stress level suggest that pomegranates could simultaneously modulate the stress response by activating several targets. For the present review, scientific evidence was gathered to integrate it and suggest a possible pathway for mediators to be involved in the mechanisms of action of the pomegranate’s antidepressant- and anxiolytic-like effects. Furthermore, the potential benefits are discussed on comorbid conditions with anxiety and depression, such as perimenopause transition and pain. Full article

Accumulating evidence suggests an involvement of sphingolipids, vital components of cell membranes and regulators of cellular processes, in the pathophysiology of both Parkinson’s disease and major depressive disorder, indicating a potential common pathway in these neuropsychiatric conditions. Based on this interaction of sphingolipids and synuclein proteins, we explored the gene expression patterns of α-, β-, and γ-synuclein in a knockout mouse model deficient for acid sphingomyelinase (ASM), an enzyme catalyzing the hydrolysis of sphingomyelin to ceramide, and studied associations with behavioral parameters. Normalized Snca, Sncb, and Sncg gene expression was determined by quantitative PCR in twelve brain regions of sex-mixed homozygous (ASM−/−, n = 7) and heterozygous (ASM+/−, n = 7) ASM-deficient mice, along with wild-type controls (ASM+/+, n = 5). The expression of all three synuclein genes was brain region-specific but independent of ASM genotype, with β-synuclein showing overall higher levels and the least variation. Moreover, we discovered correlations of gene expression levels between brain regions and depression- and anxiety-like behavior and locomotor activity, such as a positive association between Snca mRNA levels and locomotion. Our results suggest that the analysis of synuclein genes could be valuable in identifying biomarkers and comprehending the common pathological mechanisms underlying various neuropsychiatric disorders. Full article

Affective lability, a trait related to borderline personality disorder, bipolar disorder, eating disorders, and post-traumatic stress disorder, is associated with a higher number of lifetime sex partners. Among individuals who are affectively labile, boredom proneness, which has been linked to impulsive and risky sexual behaviors, might increase the likelihood of having more sex partners. Conversely, mindfulness has been found to be associated with healthy emotion regulation and lower impulsivity, and may enable a greater tolerance of affective lability and boredom, and, in turn, lower the sense of urgency to engage in sex to cope. Thus, the present study investigated the links between affective lability, boredom proneness, mindfulness, and number of sex partners in the last year. We predicted that affective lability would be positively associated with number of sex partners, and that this association would be moderated by boredom proneness and mindfulness in a three-way interaction. Adult women (N = 469, M_age = 25.15 years) were recruited from online communities and completed measures of affective lability, boredom proneness, trait mindfulness, and number of sex partners in the last year. None of the preregistered three-way interactions were supported; however, exploratory analyses revealed that, among women who reported rapid changes between depression and elation, those who were less likely to observe thoughts and sensations had more sex partners in the last year. Clinicians and researchers should further investigate which facets of mindfulness may protect against a higher number of sex partners in affectively labile individuals. Full article

Corticotropin-releasing factor (CRF) is a key neuropeptide hormone that is secreted from the hypothalamus. It is the master hormone of the HPA axis, which orchestrates the physiological and behavioral responses to stress. Many disorders, including anxiety, depression, addiction relapse, and others, are related to over-activation of this system. Thus, new molecules that may interfere with CRF receptor binding may be of value to treat neuropsychiatric stress-related disorders. Also, CRF₁R antagonists have recently emerged as potential treatment options for congenital adrenal hyperplasia. Previously, several series of CRF₁ receptor antagonists were developed by our group. In continuation of our efforts in this direction, herein we report the synthesis and biological evaluation of a new series of CRF₁R antagonists. Representative compounds were evaluated for their binding affinities compared to antalarmin. Four compounds (2, 5, 20, and 21) showed log IC₅₀ values of −8.22, −7.95, −8.04, and −7.88, respectively, compared to −7.78 for antalarmin. This result indicates that these four compounds are superior to antalarmin by 2.5, 1.4, 1.7, and 1.25 times, respectively. It is worth mentioning that compound 2, in terms of IC₅₀, is among the best CRF₁R antagonists ever developed in the last 40 years. The in silico physicochemical properties of the lead compounds showed good drug-like properties. Thus, further research in this direction may lead to better and safer CRF receptor antagonists that may have clinical applications, particularly for stress-related disorders and the treatment of congenital adrenal hyperplasia. Full article

Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/βCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/βCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/βCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice’s expression of stress-related inflammatory cytokines (IL-1β, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/βCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/βCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1β levels. The effects of the NEO/βCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress. Full article

Endometriosis, often associated with chronic pelvic pain, can lead to anxiety and depression. This study investigates the role and mechanism of Glycine receptor alpha 3 (Glrα3) in the central sensitization of pain in endometriosis, aiming to identify new therapeutic targets. Using a Glrα3 knockout mouse model of endometriosis, we employed behavioral tests, qPCR, immunofluorescence, Nissl staining, MRI, and Western blot to assess the involvement of Glrα3 in central pain sensitization. Our results indicate that endometriosis-induced hyperalgesia and anxiety–depressive-like behaviors are linked to increased Glrα3 expression. Chronic pain in endometriosis leads to gray matter changes in the sensory and insular cortices, with Glrα3 playing a significant role. The inhibition of Glrα3 alleviates pain, reduces neuronal abnormalities, and decreases glial cell activation. The absence of Glrα3 effectively regulates the central sensitization of pain in endometriosis by inhibiting glial cell activation and maintaining neuronal stability. This study offers new therapeutic avenues for the clinical treatment of endometriosis-related pain. Full article