scholarly journals Chronic Stress-Induced Depression and Anxiety Priming Modulated by Gut-Brain-Axis Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Susan Westfall ◽  
Francesca Caracci ◽  
Molly Estill ◽  
Tal Frolinger ◽  
Li Shen ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Behavioral Responses ◽  
Depression And Anxiety ◽  
Behavioral Impairment ◽  
Behavioral Deficits ◽  
Machine Learning Model ◽  
Promising Therapeutic Target ◽  
Behavioral Impairments ◽  
Better Than ◽  
Immunological Priming

Chronic stress manifests as depressive- and anxiety-like behavior while recurrent stress elicits disproportionate behavioral impairments linked to stress-induced immunological priming. The gut-brain-microbiota-axis is a promising therapeutic target for stress-induced behavioral impairments as it simultaneously modulates peripheral and brain immunological landscapes. In this study, a combination of probiotics and prebiotics, known as a synbiotic, promoted behavioral resilience to chronic and recurrent stress by normalizing gut microbiota populations and promoting regulatory T cell (Treg) expansion through modulation of ileal innate lymphoid cell (ILC)3 activity, an impact reflecting behavioral responses better than limbic brain region neuroinflammation. Supporting this conclusion, a multivariate machine learning model correlatively predicted a cross-tissue immunological signature of stress-induced behavioral impairment where the ileal Treg/T helper17 cell ratio associated to hippocampal chemotactic chemokine and prefrontal cortex IL-1β production in the context of stress-induced behavioral deficits. In conclusion, stress-induced behavioral impairments depend on the gut-brain-microbiota-axis and through ileal immune regulation, synbiotics attenuate the associated depressive- and anxiety-like behavior.

scholarly journals Sensitization to Chronic Stress-Induced Depression and Anxiety Modulated by Gut-Brain-Axis Immunity

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1174-1174
Author(s):  
Giulio Pasinetti
Keyword(s):  
Chronic Stress ◽  
Brain Regions ◽  
Multivariate Adaptive Regression Splines ◽  
Depression And Anxiety ◽  
Behavioral Impairment ◽  
Funding Sources ◽  
Adaptive Immune Cells ◽  
Promising Therapeutic Target ◽  
Adaptive Regression ◽  
Neuro Inflammation

Abstract Objectives Chronic stress manifests as depressive- and anxiety-like impairments while recurrent stress elicits disproportionate psychiatric responses linked to stress-induced immunological priming. The microbiota-gut-brain-axis is a promising therapeutic target for stress-induced behavioral impairment as it simultaneous alters the immunological landscape of the periphery and brain by modulating innate and adaptive immune cells’ activity at barrier sites. Methods Immunophenotyping of the ileum, spleen and PBMCs verified that the synbiotic's impact on ileal barrier immunity, and not inflammatory or microglial activation in limbic brain regions, best associated to stress- and synbiotic-induced behavioral responses via the microbiota-ILC3-Treg axis. A multivariate adaptive regression splines (MARS) analysis predicted that immune responses in the brain and periphery create a cross-tissue biological signature of stress-induced behavior. Ileal and splenic IL-1 and IL-6 release and the ileal Treg/Th17 cell ratio associated to limbic chemotactic chemokine and prefrontal cortex IL-1 release, which associated to behavioral deficits. Results In this study, a combination of probiotics and prebiotics (i.e., synbiotic) promoted behavioral resilience to chronic and recurrent stress by promoting regulatory T cell (Treg) activation and reducing the T helper (Th)17 to Treg ratio by modulating ileal innate lymphoid cell (ILC)3 activity. Synbiotics also normalized gut microbiome diversity and composition in response to stress while interactions of the genera Lactobacillus with Faecalibaculum, Blautia or Bifidobacterium spp. best associated to depressive-like behavior during the stress protocol. Conclusions This analysis shows how resilience to stress-induced behavioral impairment depends on the gut-brain-axis and that synbiotics indiscriminately attenuate peripheral- and neuro-inflammation associated with chronic and recurrent stress-induced depression and anxiety. Funding Sources Grant AT008661 from the NIH's ODS and the NCCIH.

scholarly journals Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

2021 ◽  
Author(s):  
Fabiola De Marchi ◽  
◽  
Claudia Carrarini ◽  
Antonio De Martino ◽  
Luca Diamanti ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Time Course ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Multisystem Disorder ◽  
Behavioral Impairment ◽  
Behavioral Impairments ◽  
Als Patients ◽  
Disease Stages ◽  
Lateral Sclerosis

Abstract Background and aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. Conclusions To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

scholarly journals 3,6′-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury

2021 ◽  
Vol 22 (15) ◽  
pp. 8276
Author(s):  
Pen-Sen Huang ◽  
Ping-Yen Tsai ◽  
Ling-Yu Yang ◽  
Daniela Lecca ◽  
Weiming Luo ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Short Term Memory ◽  
Post Injury ◽  
Behavioral Deficits ◽  
Cognitive Behaviors ◽  
Moderate Traumatic Brain Injury ◽  
Short And Long Term ◽  
Behavioral Impairments ◽  
Hippocampal Neurodegeneration

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.

scholarly journals COVID-19 pandemic related long-term chronic stress on the prevalence of depression and anxiety in the general population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tian Qi ◽  
Ting Hu ◽  
Qi-Qi Ge ◽  
Xiao-Na Zhou ◽  
Jia-Mei Li ◽  
...  
Keyword(s):  
Mental Health ◽  
General Population ◽  
Chronic Stress ◽  
Protective Factor ◽  
Mental Health Problems ◽  
Anxiety Symptoms ◽  
Binary Logistic Regression Analysis ◽  
Depression And Anxiety ◽  
Factors Associated

Abstract Background The COVID-19 pandemic has lasted for more than 1 year, causing far-reaching and unprecedented changes in almost all aspects of society. This study aimed to evaluate the long-term consequences of the COVID-19 pandemic on depression and anxiety, and explore the factors associated with it. Methods A cross-sectional study using an online survey was conducted to assess mental health problems from February 2 to February 9, 2021 by using patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7). The insomnia severity index (ISI), demographic data and COVID-19 related variables were measured by a self-designed questionnaire. The factors associated with depressive and anxiety symptoms were identified by Pearson chi-square test and binary logistic regression analysis. Results In the study that 1171 participants enrolled, the overall prevalence of depressive and anxiety symptoms among general people was 22.6 and 21.4% respectively in the present study. Living alone was a potential risk factor for depressive symptoms, while regular exercises was a potential protective factor. The prevalence of depressive and anxiety symptoms was significantly associated with the severity of insomnia symptoms and the negative feelings about pandemic. Conclusion COVID-19 pandemic- related chronic stress has brought about profound impacts on long-term mental health in the general population. The level of insomnia and a negative attitude towards the pandemic are significantly correlated with unfavorable mental health. However, we failed to found a significant association of age and gender with the mental health symptoms, although they were recognized as well-established risk factors during the outbreak by some other studies. This discrepancy may be because the acute and chronic effects of the pandemic are influenced by different factors, which reminds that more attention should be paid to the intrinsic psychological factors and physical reactions towards COVID-19.

scholarly journals Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex

2021 ◽  
Author(s):  
Sierra A. Codeluppi ◽  
Dipashree Chatterjee ◽  
Thomas D. Prevot ◽  
Keith A. Misquitta ◽  
Etienne Sibille ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Chronic Stress ◽  
Fluorescent Protein ◽  
Glial Fibrillary Acid Protein ◽  
Behavioral Deficits ◽  
Sholl Analysis ◽  
Acid Protein ◽  
Potential Link ◽  
Green Fluorescent ◽  
Stress Models

AbstractBackgroundNeuromorphological changes are consistently reported in the prefrontal cortex (PFC) of patients with stress-related disorders and in rodent stress models, but the effects of stress on astrocyte morphology and potential link to behavioral deficits are relatively unknown.MethodsTo answer these questions, transgenic mice expressing green fluorescent protein (GFP) under the glial fibrillary acid protein (GFAP) promotor were subjected to 7, 21 or 35 days of chronic restraint stress (CRS). CRS behavioral effects on anhedonia- and anxiety-like behaviours were measured using the sucrose intake and the PhenoTyper tests, respectively. PFC GFP+ or GFAP+ cells morphology was assessed using Sholl analysis and associations with behavior were determined using correlation analysis.ResultsCRS-exposed mice displayed anxiety-like behavior at 7, 21 and 35 days and anhedonia-like behavior at 35 days. Analysis of GFAP+ cell morphology revealed significant atrophy of distal processes following 21 and 35 days of CRS. CRS induced similar decreases in intersections at distal radii for GFP+ cells, accompanied by increased proximal processes. Additionally, the number of intersections at the most distal radius step significantly correlated with time spent in the shelter zone in the PhenoTyper test (r=-0.581, p<0.01) for GFP+ cells and with behavioural emotionality calculated by z-scoring all behavioral measured deficits, for both GFAP+ and GFP+ cells (r=-0.400, p<0.05; r=-0.399, p<0.05).ConclusionChronic stress exposure induces a progressive atrophy of cortical astroglial cells, potentially contributing to maladaptive neuroplastic changes associated with stress-related disorders.

scholarly journals Pair-housing of male and female rats during chronic stress exposure results in gender-specific behavioral responses

2005 ◽  
Vol 47 (5) ◽  
pp. 620-628 ◽  
Author(s):  
C. Westenbroek ◽  
T.A.B. Snijders ◽  
J.A. den Boer ◽  
M. Gerrits ◽  
D.S. Fokkema ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Behavioral Responses ◽  
Female Rats ◽  
Stress Exposure ◽  
Male And Female ◽  
Male And Female Rats ◽  
Gender Specific

scholarly journals Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

2012 ◽  
Vol 109 (28) ◽  
pp. 11378-11383 ◽  
Author(s):  
H. Son ◽  
M. Banasr ◽  
M. Choi ◽  
S. Y. Chae ◽  
P. Licznerski ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Behavioral Deficits

scholarly journals Orphan receptor GPR158 controls stress-induced depression

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Laurie P Sutton ◽  
Cesare Orlandi ◽  
Chenghui Song ◽  
Won Chan Oh ◽  
Brian S Muntean ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Molecular Mechanisms ◽  
Human Subjects ◽  
Orphan Receptor ◽  
Dependent Manner ◽  
Depression And Anxiety ◽  
Major Depressive ◽  
Protein Levels ◽  
Pharmacological Target ◽  
Decisive Action

Stress can be a motivational force for decisive action and adapting to novel environment; whereas, exposure to chronic stress contributes to the development of depression and anxiety. However, the molecular mechanisms underlying stress-responsive behaviors are not fully understood. Here, we identified the orphan receptor GPR158 as a novel regulator operating in the prefrontal cortex (PFC) that links chronic stress to depression. GPR158 is highly upregulated in the PFC of human subjects with major depressive disorder. Exposure of mice to chronic stress also increased GPR158 protein levels in the PFC in a glucocorticoid-dependent manner. Viral overexpression of GPR158 in the PFC induced depressive-like behaviors. In contrast GPR158 ablation, led to a prominent antidepressant-like phenotype and stress resiliency. We found that GPR158 exerts its effects via modulating synaptic strength altering AMPA receptor activity. Taken together, our findings identify a new player in mood regulation and introduce a pharmacological target for managing depression.

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