Chronic Stress Research Articles

Npbwr1 signaling mediates fast antidepressant action.

Chronic stress is a major risk factor for depression, a leading cause of disability and suicide. Because current antidepressants work slowly, have common side effects, and are only effective in a minority of patients, there is an unmet need to identify the underlying molecular mechanisms. Here, we identify the receptor for neuropeptides B and W, Npbwr1, as a key regulator of depressive-like symptoms. Npbwr1 is increased in the nucleus accumbens of chronically stressed mice and postmortem in patients diagnosed with depression. Using viral-mediated gene transfer, we demonstrate a causal link between Npbwr1, dendritic spine morphology, the biomarker Bdnf, and depressive-like behaviors. Importantly, microinjection of the synthetic antagonist of Npbwr1, CYM50769, rapidly ameliorates depressive-like behavioral symptoms and alters Bdnf levels. CYM50769 is selective, well tolerated, and shows effects up to 7 days after administration of a single dose. In summary, these findings advance our understanding of mood and chronic stress and warrant further investigation of CYM50769 as a potential fast-acting antidepressant.

Yeast Extract Peptides Alleviate Depression in Chronic Restraint Stress Rats by Alleviating Hippocampal Neuronal Apoptosis and Dysbiosis of the Gut Microbiota.

Depression as a global neurological disorder, and hippocampal neuronal apoptosis and disorders of the gut microbiota are closely related to it. This study aims to expose the ameliorative effect of enzyme peptides (AP) from brewer's yeast on depressive behavior caused by chronic restraint stress (CRS) in rats. After 4 weeks of AP intervention, a significant alleviation of depressive behavior in the sucrose preference test (SPT), forced swim test (FST), and light-dark test (LDT) is observed in depressed rats. AP ameliorates neuronal damage with increased the expression of the key CREB/BDNF/TrkB/Akt signaling pathway, which increases the levels of the monoamine neurotransmitters 5-hydroxytryptamine (5-HT) and norepinephrine (NE) in the hippocampus, buffering hyperactivity of the hypothalamo-pituitary-adrenal axis (HPA), and decreasing the serum cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in rats. In addition, AP modulates the disruption of the rat gut microbiota by chronic restraint stress (CRS), and the changes in the abundance of Lactobacillus animalis and Lactobacillus johnsonii are probably the key for AP performing antidepressant benefits. A strong correlation is found between gut microbiota and biochemical markers of depression. AP, as a natural and safe active substance, has a positive effect in the treatment of depression.

Extremely Low-Frequency Electromagnetic Field (ELF-EMF) Increases Mitochondrial Electron Transport Chain Activities and Ameliorates Depressive Behaviors in Mice.

Compromised mitochondrial electron transport chain (ETC) activities are associated with depression in humans and rodents. However, the effects of the enhancement of mitochondrial ETC activities on depression remain elusive. We recently reported that an extremely low-frequency electromagnetic field (ELF-EMF) of as low as 10 μT induced hormetic activation of mitochondrial ETC complexes in human/mouse cultured cells and mouse livers. Chronic social defeat stress (CSDS) for 10 consecutive days caused behavioral defects mimicking depression in mice, and using an ELF-EMF for two to six weeks ameliorated them. CSDS variably decreased the mitochondrial ETC proteins in the prefrontal cortex (PFC) in 10 days, which were increased by an ELF-EMF in six weeks. CSDS had no effect on the mitochondrial oxygen consumption rate in the PFC in 10 days, but using an ELF-EMF for six weeks enhanced it. CSDS inactivated SOD2 by enhancing its acetylation and increased lipid peroxidation in the PFC. In contrast, the ELF-EMF activated the Sirt3-FoxO3a-SOD2 pathway and suppressed lipid peroxidation. Furthermore, CSDS increased markers for mitophagy, which was suppressed by the ELF-EMF in six weeks. The ELF-EMF exerted beneficial hormetic effects on mitochondrial energy production, mitochondrial antioxidation, and mitochondrial dynamics in a mouse model of depression. We envisage that an ELF-EMF is a promising therapeutic option for depression.

Ethogram of the Domestic Cat

The existing domestic cat literature predominantly contains lists detailing its behaviour. However, these lists are neither specific enough for domestic cats nor general enough for all behaviours on a macro level of the domestic cat. Furthermore, the majority of studies lack illustrations. Therefore, we have developed a comprehensive ethogram of the domestic cat and scalable schematic representations of the behaviour units. We evaluated observational data from free-roaming cats and cats from private households using ad libitum and focal animal sampling (video material 55.31 h, n = 170 animals). In addition, we used the leading literature and detailed anatomical studies to create systematic categories and morphologically correct drawings. A total of 117 discrete behaviours were recorded and divided into 12 categories. The description of each behaviour includes a name, a word definition, an ethological classification and a schematic illustration (excluding the category devoted to vocalisations). An ethogram is needed to better understand the behavioural repertoire of healthy domestic cats and to facilitate the design phase of further investigations. This document can help to better distinguish species-appropriate behaviours and body postures from those behaviours and poses that indicate chronic pain, stress or discomfort.

Effects of Ovarian Stimulation with Gonadotropins in the Conditions of Chronic Psychosocial Stress on the Quality of Murine Oocyte

Chronic psychosocial stress may negatively affect the female reproductive system. Meanwhile, the effect of ovarian stimulation with gonadotropins during stress on the quality of oocytes remains poorly studied. The purpose of this work was to investigate the effects of chronic psychosocial stress on the quality of murine cumulus-oocyte complexes during natural estrus cycle, as well as during ovarian stimulation with exogenous gonadotropins; the latter is an important part of modern assisted reproductive technologies. The results of the study demonstrate that psychosocial stress does not affect the number of ovulating oocytes, but worsens their quality, i. e. reduces the percentage of mature oocytes. In addition, stressed mice exhibited the increased accumulation of reactive oxygen species in oocytes, which is accompanied by the enhanced rate of apoptosis in cumulus cells. Hormonal stimulation of the ovaries with gonadotropins alleviates the negative changes associated with the psychosocial stress, normalizing the level of reactive oxygen species in oocytes and reducing the rate of apoptosis in cumulus cells.

Extracellular vesicles and citrullination signatures are novel biomarkers in sturgeon (Acipenser gueldenstaedtii) during chronic stress due to seasonal temperature challenge

Acipenser gueldenstaedtii is one of the most cultured sturgeon species worldwide and of considerable economic value for caviar production. There are though considerable challenges around chronic stress responses due to increased summer temperatures, impacting sturgeons’ immune responses and their susceptibility to opportunistic infections. The identification of molecular and cellular pathways involved in stress responses may contribute to identifying novel biomarkers reflective of fish health status, crucial for successful sturgeon aquaculture. Protein citrullination is a calcium-catalysed post-translational modification caused by peptidylarginine deiminases (PADs), altering target protein function and affecting protein interactions in physiological and pathobiological processes. PADs can also modulate extracellular vesicle (EVs) profiles, which play critical roles in cellular communication, via transport of their cargoes (proteins, including post-translationally modified proteins, genetic material and micro-RNAs).This study identified differences in EV signatures, and citrullinated proteins in sera from winter and summer farmed sturegeons. EVs were significantly elevated in sera of the summer chronically stressed group. The citrullinated proteins and associated gene ontology (GO) pathways in sera and serum-EVs of chronically heat stressed A. gueldenstaedtii, showed some changes, with specific citrullinated serum protein targets including alpa-2-macroglobulin, alpha globin, calcium-dependent secretion activator, ceruloplasmin, chemokine XC receptor, complement C3 isoforms, complement C9, plectin, selenoprotein and vitellogenin. In serum-EVs, citrullinated protein cargoes identified only in the chronically stressed summer group included alpha-1-antiproteinase, apolipoprotein B-100, microtubule actin crosslinking factor and histone H3. Biological gene ontology (GO) pathways related to citrullinated serum proteins in the chronically stressed group were associated with innate and adaptive immune responses, stress responses and metabolic processes. In serum-EVs of the heat-stressed group the citrullinome associated with various metabolic GO pathways.In addition to modified citrullinated protein content, Serum-EVs from the stressed summer group showed significantly increased levels of the inflammatory associated miR-155 and the hypoxia-associated miR-210, but significantly reduced levels of the growth-associated miR-206.Our findings highlight roles for protein citrullination and EV signatures in response to chronic heat stress in A. gueldenstaedtii, indicating a trade-off in immunity versus growth and may be of value for sturgeon aquaculture.

Long-term, dynamic remodelling of the corticotroph transcriptome and excitability after a period of chronic stress.

Chronic stress results in long-term dynamic changes at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis resulting in stress axis dysregulation with long term impacts on human and animal health. However, the underlying mechanisms and dynamics of altered of HPA axis function, in particular at the level of pituitary corticotrophs, during a period of chronic stress and in the weeks after its cessation (defined as "recovery") are very poorly understood. Here we address the fundamental question of how a period of chronic stress results in altered anterior pituitary corticotroph function and whether this persists in recovery, as well as the transcriptomic changes underlying this. We demonstrate that in mice spontaneous and corticotrophin releasing hormone (CRH)-stimulated electrical excitability of corticotrophs, essential for ACTH secretion, is suppressed for weeks-months of recovery following a period of chronic stress. Surprisingly, there are only modest changes in the corticotroph transcriptome during the period of stress but major alterations occur in recovery. Importantly, while transcriptional changes for a large proportion of mRNAs follow the time course suppression of corticotroph excitability, many other genes display highly dynamic transcriptional changes with distinct time courses throughout recovery. Taken together, this suggests that chronic stress results in complex dynamic transcriptional and functional changes in corticotroph physiology, which are highly dynamic for weeks following cessation of chronic stress. These insights provide a fundamental new framework to further understand underlying molecular mechanisms as well approaches to both diagnosis and treatment of stress-related dysfunction of the HPA axis.

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

BackgroundAsiaticoside, 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.MethodsBehavioral 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.ResultsThis 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.ConclusionsThese results suggested that asiaticoside exerts antidepressant effects through the microbiota-gut-brain axis in a CUMS mouse model.

'Impaired in life': Analyzing people's accounts of depression in Ethiopia - Implications for a cultural-eco social approach to global mental health.

Depression is a global crisis and a major concern in mental health interventions, particularly in low- and middle-income countries (LMICs), where it significantly impacts disability, quality of life, and economic stability. These chronic stressors have been used to argue for scaling up the detection and treatment of depression as a public health and development priority. This study aimed to explore illness narratives of depression among patients' and to gain insights into multifaceted suffering, its impact on persons' lives, and help seeking. This study is part the broader study which examined global mental health, biopolitics, and depression in Ethiopia, conducted in hospice setting to explore the conception of depression in Bahirdar city, Northern Ethiopia, among patients and health care providers. In this study, we focus on patients' accounts of depression. We employed an ethnography method using in-depth interviews, fieldnotes, and observation to collect the data. A thematic analysis was used to analyze the data. Drawing from cross-cultural and critical psychiatry perspectives, we situate depression within its cultural-eco social framework. The study revealed that patients' experiences and conception of depression are deeply intertwined with Ethiopia's sociocultural, economic, and spiritual context. Depression was often described as a state of being 'impaired in life', reflecting the complex interplay of individual struggles and societal pressures. Integrating quotes from patients, we demonstrated in this analysis the ways in which biographically specific challenges, societal pressures, and mental well-being are understood by study participants in accordance with Ethiopian cultural and religious norms. The study suggests moving beyond narrow interpretative frameworks in GMH praxis to understand and address the complex dimensions of depression in Ethiopia and similar contexts. The study advocates for a cultural-ecosocial approach to depression, emphasizing the need for mental health interventions that consider the broader social and cultural factors contributing to mental distress.

Limosilactobacillus-related 3-OMDP as a potential therapeutic target for depression

Objective Gut microbiota was closely involved in the pathogenesis of depression, but the underlying molecular mechanisms in depression remained unclear. This study was conducted to investigate the relationship between neurotransmitters/inflammatory factors and gut microbiota in depressed mice. Materials and methods A chronic social defeat stress (CSDS) depression model was established. Gut microbial composition was detected in faeces, neurotransmitters were detected in faeces, colon, blood and hippocampus, and inflammatory factors were detected in hippocampus. After a key neurotransmitter was identified, intervention experiment was conducted to explore whether it could improve depressive-like behaviours. Results Six differential genera in faeces, 14 differential neurotransmitters in gut-brain axis, and two differential inflammatory factors (interleukin-1 beta (IL-1β) and interleukin-6 (IL-6)) in hippocampus were identified in depressed mice. There were significant correlations among differential genera, differential neurotransmitters and IL-1β/IL-6. Among these differential neurotransmitters, 3-O-Methyldopa (3-OMDP) was found to be consistently decreased in faeces, colon, blood and hippocampus, and 3-OMDP was significantly correlated to Limosilactobacillus and IL-1β. After receiving 3-OMDP, the depressive-like behaviours in depressed mice were improved and the increased IL-1β/IL-6 levels were reversed. Conclusions These results indicated that gut microbiota might affect host’s inflammation levels in brain through regulating neurotransmitters, eventually leading to the onset of depression. ‘Limosilactobacillus-3-OMDP-IL-1β/IL-6’ might be a potential pathway in the crosstalk of gut and brain, and 3-OMDP held the promise as a therapeutic target for depression.

"Hanging on by a Thread": The Lived Experience of Parents of Children with Medical Complexity.

Families with children with medical complexity endure high levels of chronic and toxic stress, impacting the overall health and wellbeing of all family members and the system as a whole. The purpose of this study was to examine the lived experiences of parents/caregivers with children with medical complexity. The lived experiences of 15 parents of children with complex medical needs were explored using focus group discussions. Focus group discussions were recorded, transcribed, and analyzed using van Manen's 6-step process for hermeneutic phenomenology. Aligned with the research questions, the analysis draws on van Manen's four lived existential analytical categories. Themes include: (1) lived body, the psychological and physiological effect; (2) lived time and space, the immediate impact on the there, now, and then; (3) lived relationships, social life and family relational effect; (4) risk factors; and (5) protective factors. Caregivers of children with medical complexity have a unique experience of trauma and resilience. This study will inform interdisciplinary medical providers about the mental health and resiliency experiences of this population to support more effective healthcare practices.

Understanding the Antidepressant Mechanisms of Acupuncture: Targeting Hippocampal Neuroinflammation, Oxidative Stress, Neuroplasticity, and Apoptosis in CUMS Rats.

Depression is recognized globally as one of the most intractable diseases, and its complexity and diversity make treatment extremely challenging. Acupuncture has demonstrated beneficial effects in various psychiatric disorders. However, the underlying mechanisms of acupuncture's antidepressant action, particularly in depression, remain elusive. Therefore, this study aimed to investigate the effects of acupuncture on chronic unpredictability stress (CUMS)-induced depressive symptoms in rats and to further elucidate its underlying molecular mechanisms. All rats were exposed to CUMS of two stressors every day for 28 days, except for the control group. One hour before CUMS, rats were given a treatment with acupuncture, electroacupuncture, sham-acupuncture, or fluoxetine (2.1 mg/kg). Behavioral tests and biological detection methods were conducted in sequence to evaluate depression-like phenotype in rats. The findings of this study demonstrate that acupuncture therapy effectively ameliorated depression-like behavior induced by CUMS in rats. Additionally, acupuncture exerted a restorative effect on the alterations induced by CUMS in the levels of malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), brain-derived neurotrophic factor (BDNF), cyclic AMP response element-binding protein (CREB), postsynaptic density95 (PSD95), gamma-aminobutyric acid (GABA), and acetylcholine (ACh). Additionally, our findings indicate that acupuncture also modulates the ERK and Caspase-3 apoptotic pathways in the hippocampus of CUMS rats. This study suggests that acupuncture may play a potential preventive role by regulating hippocampal neuroinflammatory response, levels of oxidative stress, apoptotic processes, and enhancing synaptic plasticity.

HOUSING TEMPERATURE ALTERS BURN INDUCED HYPERMETABOLISM IN MICE.

Mice used in biomedical research are typically housed at ambient temperatures (22-24 °C) below thermoneutrality (26-31 °C). This chronic cold stress triggers a hypermetabolic response that may limit the utility of mice in modeling hypermetabolism in response to burns. To evaluate the effect of housing temperature on burn-induced hypermetabolism, mice were randomly assigned to receive sham, small, or large scald burns. Mice recovered for 21 days in metabolic phenotyping cages at 24 °C or 30 °C. Regardless of sex or sham/burn treatment, mice housed at 24 °C had greater total energy expenditure (TEE, P < 0.001), which was largely attributable to greater basal energy expenditure (BEE) when compared to mice housed at 30 °C (P < 0.001). Thermoneutral housing (30 °C) altered adipose tissue mass in a sex-dependent manner. Compared to sham and small burn groups, large burns resulted in greater water vapor loss, regardless of housing temperature (P < 0.01). Compared to sham, large burns resulted in greater BEE and TEE in mice housed at 24 °C, however, this hypermetabolic response to large burns was blunted in female mice housed at 30 °C, and absent in male mice housed at 30 °C. Locomotion was significantly reduced in mice with large burns compared to sham and small burn groups, irrespective of sex or housing temperature (P < 0.05). Housing at 30 °C revealed sexual dimorphism in terms of the impact of burns on body mass and composition, where males with large burns displayed marked cachexia, whereas females did not. Collectively, this study demonstrates a sex-dependent role for housing temperature in influencing energetics and body composition in a rodent model of burn trauma.

Examining the association between psychological resilience and chronic versus discrete stressors among individuals who use opioids in Baltimore, Maryland.

Psychological resilience has emerged as a key construct of interest in the study of substance use. However, very few studies have examined resilience among individuals who are actively using drugs. Furthermore, many studies of psychological resilience have focused on individual-level factors. This study addresses the call for a more 'ecological' approach to the study of resilience by exploring how socio-structural vulnerabilities may shape individuals' assessment of their own ability to cope. The Peer Harm Reduction of Maryland Outreach Tiered Evaluation study conducted a cross-sectional survey of people who used opioids in Baltimore, Maryland, USA (n = 565). Resilience was measured using the 10-item Connor-Davidson Resilience Scale. We used linear regression to examine the association between resilience and stressors commonly encountered by individuals who use drugs, including both chronic, enduring stressors (e.g., homelessness, food insecurity) and discrete, event-based stressors (e.g., overdose, arrest). We observed a negative relationship between self-reported resilience and chronic stressors. Specifically, individuals who reported experiencing three (β = -4.08; p = 0.002) or four (β = -4.67; p = 0.008) types of chronic stress had significantly lower resilience scores. Additionally, we found that an unmet need for mental health treatment was associated with reduced resilience (β = -1.74; p = 0.040) and greater educational attainment was associated with increased resilience (β = 2.13; p = 0.005). Overlapping experiences of socio-structural vulnerability, as well as access to mental health care, may influence how individuals who use drugs evaluate their own resilience. Interventions that seek to promote the resilience of this population should focus on addressing structural drivers of marginalisation and barriers to mental health treatment.

Design of a Mindfulness intervention to reduce risk factors for colorectal cancer among at-risk Black women in Chicago.

Chronic stress can directly and indirectly promote carcinogenesis through immune, metabolic, and microbial pathways. Our overarching hypothesis is that reducing chronic stress will have important implications for colorectal cancer (CRC) risk reduction among vulnerable and high-risk populations. A promising approach for reducing chronic stress is Mindfulness. Mindfulness is a meditation-based technique that achieves a state of mind that is used to experience higher awareness or consciousness. Existing small studies suggest Mindfulness can positively regulate stress response in a way that translates to anti-cancer effects, including reduced systemic inflammation. We propose to evaluate an 8-week Mindfulness intervention delivered in a hybrid format (synchronous and asynchronous sessions) among 40 Black women at elevated risk of CRC who reside in vulnerable communities and who report moderate to high perceived stress. At baseline and post-intervention, participants will provide blood, hair, and stool, undergo body composition analysis, and complete mood and lifestyle-related surveys. The specific aims are to assess the feasibility and acceptability of the intervention and explore changes on stress, weight, fasting glucose, inflammation markers, and the gut microbiota - risk markers and risk pathways associated with CRC. The data generated through this project will inform if Mindfulness is a feasible option for CRC risk reduction among high-risk individuals.

Female Specific Restrictive Cardiomyopathy and Metabolic Dysregulation in transgenic mice expressing a Peptide of the Amino-Terminus of GRK2.

Cardiovascular disease and heart failure are a major health challenge, with sex differences in pathophysiology and treatment responses critically influencing patient outcomes. G protein-coupled receptor (GPCR) kinase 2 (GRK2) is a pivotal regulator of cellular signaling whose elevation is a hallmark of heart failure progression. Its complex network of protein interactions impact a wide range of physiological and pathophysiological processes including cardiac function. In this study, we examined the effects of cardiac-restricted expression of an amino-terminal peptide of GRK2 (βARKnt) in female mice subjected to acute and chronic pressure overload. Our findings reveal that that βARKnt affects hypertrophy development and cardiac function differently in female mice than in males, leading to a transition to heart failure not observed in control females or βARKnt males. Notably, the βARKnt female mice exhibited baseline hypertrophy with distinct left atrial morphology, increased fibrosis, and immune cell infiltration compared to the controls, which progressed under chronic stress, indicating adverse cardiac remodeling. Furthermore, βARKnt female mice, unlike males, exhibit impaired tissue respiration following acute pressure overload and altered glucose sensitivity and insulin tolerance, highlighting significant remodeling of cardiac and systemic metabolism.

Communicatively constructing resilience: Exploring family resilience in the experience of hereditary cancer

AbstractObjectiveThe goal was to explore how families communicate to cope with hereditary cancer conditions and identify factors that may enhance resilience and recommended decision‐making.BackgroundFamilies with Hereditary Breast and Ovarian Cancer syndrome (HBOC), Lynch syndrome (LS), and Li‐Fraumeni syndrome (LFS) have an increased lifetime risk of developing cancer. We use the communication theory of resilience (CTR) to examine how families engage in resilience and make health decisions about hereditary cancer risks over time.MethodWe conducted 42 dyadic interviews with families with HBOC, LS, and LFS. Themes emerged through qualitative analysis for each of the resilience processes outlined by CTR (crafting normalcy, communication networks, identity anchors, alternative logics, and foregrounding productive action while legitimizing negative feelings), illustrating how family members manage stressors associated with hereditary cancer over time.ResultsParticipants described enacting each of the five CTR processes to manage the acute and chronic stressors associated with hereditary cancer. We described themes that emerged within each of the five resilience processes.ConclusionFindings demonstrate the ways in which families managing hereditary cancer risks enact resilience processes and how these processes may have a complex relationship to coping and medical decision‐making.ImplicationsFindings demonstrate areas for intervention to support familial resilience.

Transcriptomic analysis of rat prefrontal cortex following chronic stress induced by social isolation – Relevance to psychiatric and neurodevelopmental illness, and implications for treatment

Social isolation is an established risk factor for psychiatric illness, and became increasingly topical with the spread of SARS-CoV-2. We used RNA sequencing (RNA-Seq) to enable unbiased assessment of transcriptomic changes within the prefrontal cortex (PFC) of isolation-reared rats. To provide insight into the relevance of this manipulation for studying human illness, we compared differentially expressed genes (DEGs) and enriched biological functions against datasets involving post-mortem frontal cortical tissue from patients with psychiatric and neurodevelopmental illnesses. Sixteen male Sprague-Dawley rats were reared in groups of four or individually from weaning on postnatal day (PND) 22–24 until PFC tissue collection for RNA-Seq (PND64-66). We identified a total of 183 DEGs in isolates, of which 128 mirrored those in PFC tissue from patients with stress-related mental illnesses and/or neurodevelopmental conditions featuring social deficits. Seventy-one encode proteins classed as druggable by the gene-drug interaction database. Interestingly there are antagonists or inhibitors for the products of three of these up-regulated DEGs (Hrh3, Snca and Sod1) and agonists or activators for products of six of these down-regulated DEGs (Chrm4, Klf2, Lrrk2, Nr4a1, Nr4a3 and Prkca). Some have already undergone pre-clinical and clinical evaluation, and studies with the remainder may be warranted. Changes to Hrh3, Sod1, Chrm4, Lrrk2, Nr4a1 and Prkca were replicated in an independent cohort of sixteen male Sprague-Dawley rats via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Our findings support the continued use of post-weaning isolation rearing to investigate the neurobiology of stress-related disorders and evaluate therapeutic targets.

Cytokine Status Disorders and Their Role in the Pathogenesis of Chronic Abacterial Prostatitis of Non-Inflammatory Nature

Relevance. Chronic abacterial prostatitis (CAP) of a non-inflammatory nature remains a complex disease in terms of proven etiological factors and pathogenetic mechanisms. Recent studies define it as a nosology based on homeostasis disorders with damaging effects directed towards the prostate. Pathogenetically, this is cytokine aseptic inflammation and lipid peroxidation, which occurs under conditions of compromised antioxidant protection. Objective — to study the cytokine status in the experimental reproduction of non-inflammatory CAP models.Materials and methods. 100 male white rats were studied, 25 formed a control group, and the remaining ones were divided into 3 equal groups for experiments on creating various models of CAP and systemic chronic stress. At the end of the experiment, blood was taken and the prostate was removed to obtain a homogenate. The substrates were used to determine pro- and anti-inflammatory cytokines.Results. In the isolated CAP model of category IIIB, cytokine disorders were detected in prostate tissue (to a greater extent), and at the systemic level (to a lesser extent). The model of systemic immobilization stress proved the possibility of triggering cytokine disorders in prostate tissue characteristic of CAP IIIB. Severe homeostasis disorders at the systemic and local levels were observed in experiments where both systemic stress and the local CAP model were modeled.Conclusion. Cytokine imbalance plays a key role in the pathogenesis of СAP IIIB. At the same time, systemic and organ cytokine disorders interact with each other and, under certain circumstances, aggravate the damaging effect of each other.

Tinnitus Generation and Behavioral Changes Caused by Chronic Stress: A Behavioral and Brain Study in a Rat Model.

This study explores the connection between chronic stress and tinnitus, a phantom auditory perception, using an animal model. Rats were subjected to 2 h of daily restraint stress for 10 days. Tinnitus was assessed on the last day of stress exposure using the gap response of pre-pulse inhibition acoustic reflex, measured at 60 dB background sound level at 8, 16, and 20 kHz. Chronic stress-exposed rats were categorized into two groups: tinnitus (RTG) and non-tinnitus (RNTG). Various tests, including hearing assessments (distortion product otoacoustic emissions and auditory brainstem response), behavioral evaluations (elevated plus maze test and forced swimming test), and immunohistochemical studies in the auditory and limbic brain regions, were conducted to understand the relationship between chronic stress, tinnitus, and behavioral changes. Following chronic restraint stress, 64.3% of the rats exhibited tinnitus with no audiometric changes. EPM and FST indicated an increase of anxiety- and depression-related behavior in RTG. Immunohistochemical analyses identified specific alterations in the expression of neurotransmitter receptors within brain regions implicated in tinnitus. Specifically, we observed a decrease in γ-aminobutyric acid A receptor α1 expression and an increase in glutamate receptor (N-methyl-D-aspartate receptor subunit 1 and receptor subunit 2B) expression in specific brain region. These changes suggest a reorganization of neural circuits associated with the tinnitus generation and behavioral changes of the rats after chronic stress exposure. Chronic stress alone can be a causal factor for the generation of tinnitus and behavioral changes through altered neural activities in tinnitus-related brain networks. NA Laryngoscope, 2024.