scholarly journals Antidepressive Effects of Kamishoyosan through 5-HT1AReceptor and PKA-CREB-BDNF Signaling in the Hippocampus in Postmenopausal Depression-Model Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Shoko Shimizu ◽  
Yugo Ishino ◽  
Takashi Takeda ◽  
Masaya Tohyama ◽  
Shingo Miyata
Keyword(s):  
Postmenopausal Women ◽  
Chronic Stress ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Water Immersion ◽  
Neuropsychiatric Symptoms ◽  
Continuous Administration ◽  
Bdnf Signaling ◽  
Postmenopausal Depression

Females are well known to suffer disproportionately more than males from stress-related neuropsychiatric disorders, especially during perimenopausal and postmenopausal periods. In addition to a decline in serum estradiol levels, environmental stress and social stress likely contribute to the development of neuropsychiatric symptoms in perimenopausal and postmenopausal women. Kamishoyosan (KSS) is a traditional Japanese Kampo medicine, composed of a specified mixture of 10 crude compounds derived from plant sources, widely used for various neuropsychiatric symptoms in perimenopausal and postmenopausal women. However, the molecular mechanisms underlying KSS-mediated attenuation of neuropsychological symptoms and stress-response behaviors in perimenopausal and postmenopausal women remain unknown. In the present study, we first established a mouse model for postmenopausal depression-like signs using chronic water-immersion and restraint-stressed ovariectomized (OVX) mice to investigate the underlying molecular mechanism of KSS. We found that continuous administration of KSS to these mice normalized the activation of the hypothalamic-pituitary-adrenal (HPA) axis, ameliorated stress-induced depressive behavior, and prevented a decrease of neurogenesis in the hippocampus. As previous studies have implicated dysfunction of the hippocampal 5-HT1A receptor (5-HT1AR) in depressive disorders, we also evaluated the effect of KSS on 5-HT1AR expression and the protein kinase A- (PKA-) cAMP response element-binding- (CREB-) brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus in this model. The level of 5-HT1AR in the hippocampus decreased in chronic stress-exposed OVX mice, while KSS treatment normalized the stress-induced decrease in 5-HT1AR expression in the hippocampus of chronic stress-exposed OVX mice. Furthermore, we found that KSS treatment upregulated the expression levels of phosphorylated PKA (p-PKA), phosphorylated CREB (p-CREB), and BDNF in the hippocampus in chronic stress-exposed OVX mice. These results suggest that KSS improves neuropsychiatric symptoms through 5-HT1AR and PKA-CREB-BDNF signaling in the hippocampus in postmenopausal women.

scholarly journals Sex differences in chronic social stress models in mice

2019 ◽  
Author(s):  
Orit Furman ◽  
Michael Tsoory ◽  
Alon Chen
Keyword(s):  
Sex Differences ◽  
Animal Models ◽  
Mouse Model ◽  
Treatment Response ◽  
Chronic Stress ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Body Weight Loss ◽  
Chronic Social Stress

AbstractChronic stress creates an allostatic overload that may lead to mood disorders such as anxiety and depression. Modern causes of chronic stress in humans are mostly social in nature, relating to work and relationship stress. Research into neural and molecular mechanisms of vulnerability and resilience following chronic social stress (CSS) is ongoing and uses animal models to discover efficient prevention strategies and treatments. To date, most CSS studies have neglected the female sex and used male-focused aggression-based animal models such as chronic social defeat stress (CSDS). Accumulating evidence on sex differences suggests differences in the stress response, the prevalence of stress-related illness and the treatment response, indicating that researchers should expand CSS investigation to include female-focused protocols alongside the popular CSDS protocols. Here, we describe a novel female mouse model of CSS and a parallel modified male mouse model of CSDS in C57BL/6 mice. These new models enable the investigation of vulnerability, coping and downstream effectors mediating long-term consequences of CSS in both sexes. Our data demonstrate sex differences during CSS and for many weeks following CSS. Female mice are more prone to body weight loss during CSS and hyperactive anxious behavior following CSS. Both sexes show disturbances in social interaction, but only stressed male mice show long-term changes in neuroendocrine function and memory performance after fear conditioning. We discuss future avenues of research using these models to investigate mechanisms pertaining to sensitivity to CSS as well as treatment response profiles, in a sex-suitable manner.

scholarly journals Cold-water immersion following sprint interval training does not alter endurance signaling pathways or training adaptations in human skeletal muscle

2017 ◽  
Vol 313 (4) ◽  
pp. R372-R384 ◽  
Author(s):  
James R. Broatch ◽  
Aaron Petersen ◽  
David J. Bishop
Keyword(s):  
Mitochondrial Biogenesis ◽  
Molecular Mechanisms ◽  
Cold Water ◽  
P53 Protein ◽  
Water Immersion ◽  
Interval Training ◽  
Cold Water Immersion ◽  
Peroxisome Proliferator ◽  
Sprint Interval Training ◽  
Single Session

We investigated the underlying molecular mechanisms by which postexercise cold-water immersion (CWI) may alter key markers of mitochondrial biogenesis following both a single session and 6 wk of sprint interval training (SIT). Nineteen men performed a single SIT session, followed by one of two 15-min recovery conditions: cold-water immersion (10°C) or a passive room temperature control (23°C). Sixteen of these participants also completed 6 wk of SIT, each session followed immediately by their designated recovery condition. Four muscle biopsies were obtained in total, three during the single SIT session (preexercise, postrecovery, and 3 h postrecovery) and one 48 h after the last SIT session. After a single SIT session, phosphorylated (p-)AMPK, p-p38 MAPK, p-p53, and peroxisome proliferator-activated receptor-γ coactivator-1α ( PGC-1α) mRNA were all increased ( P < 0.05). Postexercise CWI had no effect on these responses. Consistent with the lack of a response after a single session, regular postexercise CWI had no effect on PGC-1α or p53 protein content. Six weeks of SIT increased peak aerobic power, maximal oxygen consumption, maximal uncoupled respiration (complexes I and II), and 2-km time trial performance ( P < 0.05). However, regular CWI had no effect on changes in these markers, consistent with the lack of response in the markers of mitochondrial biogenesis. Although these observations suggest that CWI is not detrimental to endurance adaptations following 6 wk of SIT, they question whether postexercise CWI is an effective strategy to promote mitochondrial biogenesis and improvements in endurance performance.

scholarly journals miR-98-5p plays a critical role in depression and antidepressant effect of ketamine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chaoli Huang ◽  
Yuanyuan Wang ◽  
Zifeng Wu ◽  
Jiali Xu ◽  
Ling Zhou ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Stress ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Rapid Onset ◽  
Therapeutic Strategies ◽  
Antidepressant Effect ◽  
Depression Treatment ◽  
Chronic Social Stress ◽  
Beneficial Effects

AbstractKetamine has been demonstrated to be a rapid-onset and long-lasting antidepressant, but its underlying molecular mechanisms remain unclear. Recent studies have emerged microRNAs as important modulators for depression treatment. In this study, we report that miR-98-5p is downregulated in the prefrontal cortex and hippocampus of mice subjected to chronic social stress, while overexpressing it by its agonist alleviates depression-like behaviors. More importantly, we demonstrate that miR-98-5p is upregulated by ketamine administration, while inhibition of it by its antagonist blocks the antidepressant effect of ketamine. Our data implicate a novel molecular mechanism underlying the antidepressant effect of ketamine, and that therapeutic strategies targeting miR-98-5p could exert beneficial effects for depression treatment.

scholarly journals Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory

2018 ◽  
Vol 115 (43) ◽  
pp. E10187-E10196 ◽  
Author(s):  
Michael A. van der Kooij ◽  
Tanja Jene ◽  
Giulia Treccani ◽  
Isabelle Miederer ◽  
Annika Hasch ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Spatial Memory ◽  
Chronic Stress ◽  
High Glucose ◽  
Social Stress ◽  
Cognitive Impairments ◽  
Memory Performance ◽  
Dietary Treatment ◽  
Metabolic Phenotype ◽  
The Brain

Stringent glucose demands render the brain susceptible to disturbances in the supply of this main source of energy, and chronic stress may constitute such a disruption. However, whether stress-associated cognitive impairments may arise from disturbed glucose regulation remains unclear. Here we show that chronic social defeat (CSD) stress in adult male mice induces hyperglycemia and directly affects spatial memory performance. Stressed mice developed hyperglycemia and impaired glucose metabolism peripherally as well as in the brain (demonstrated by PET and induced metabolic bioluminescence imaging), which was accompanied by hippocampus-related spatial memory impairments. Importantly, the cognitive and metabolic phenotype pertained to a subset of stressed mice and could be linked to early hyperglycemia 2 days post-CSD. Based on this criterion, ∼40% of the stressed mice had a high-glucose (glucose >150 mg/dL), stress-susceptible phenotype. The relevance of this biomarker emerges from the effects of the glucose-lowering sodium glucose cotransporter 2 inhibitor empagliflozin, because upon dietary treatment, mice identified as having high glucose demonstrated restored spatial memory and normalized glucose metabolism. Conversely, reducing glucose levels by empagliflozin in mice that did not display stress-induced hyperglycemia (resilient mice) impaired their default-intact spatial memory performance. We conclude that hyperglycemia developing early after chronic stress threatens long-term glucose homeostasis and causes spatial memory dysfunction. Our findings may explain the comorbidity between stress-related and metabolic disorders, such as depression and diabetes, and suggest that cognitive impairments in both types of disorders could originate from excessive cerebral glucose accumulation.

scholarly journals A-74 COVID-19 and Post-Acute Sequelae of SARS-CoV-2 Infection (PASC): Acute and Longitudinal Analysis of Anosmia and Ageusia with Delayed Sudden-Onset Neuropsychiatric Symptoms

2021 ◽  
Vol 36 (6) ◽  
pp. 1116-1116
Author(s):  
Patricia A Pimental ◽  
Anna Ciampanelli ◽  
Eisha H Vora
Keyword(s):  
Depressive Disorders ◽  
Neuropsychiatric Symptoms ◽  
Neuropsychological Testing ◽  
Sudden Onset ◽  
Diagnostic Specificity ◽  
Total Recovery ◽  
Time Period ◽  
Smell Test ◽  
History Of

Abstract Objective Patients with COVID-19 and PASC may exhibit chemosensory dysfunction associated with acute neuroinflammation from immune system overactivation (Uzunova, Pallanti, & Hollander, 2021). Neuropsychiatric disturbances in patients with no history of anxiety or depression have also been reported. These central nervous system manifestations of COVID-19 may be sequelae of trans-olfactory and infralimbic tract penetration (Speth et al., 2020). Methods Our case involved a 52-year-old, right-handed, American Indian female, who at three months post neuropsychological evaluation, was diagnosed with laboratory confirmed COVID-19 with onset of complete anosmia and ageusia. Two months later, a sudden-onset of panic and depression occurred with no precipitating event. All symptoms were documented daily until return of function. Results Pre-COVID-19 neuropsychological testing revealed findings consistent with ophthalmologic/vestibular migraine and ruled out dementia, and formal anxiety and depressive disorders. Post-COVID-19 neuropsychological analysis and follow-up revealed that anosmia and ageusia had largely resolved after 8-months, and that the delayed sudden-onset panic and depression also resolved within that same time period. Conclusions A paucity of data exists concerning COVID-19 and PASC anosmia and ageusia, and sudden-onset neuropsychiatric symptoms. Our case is unique since neuropsychological testing preceded the COVID-19 infection, which provided a baseline of functioning (e.g., Pocket Smell Test: 3/3 baseline and 0/3 acute COVID-19) and pre-morbid diagnostic specificity. The present case findings align with Cappali and Gatti (2021) whereby 91% of patients reported olfactory recovery, with 53% total recovery after 8-months. No other known reports simultaneously documented detailed recovery of anosmia, ageusia and delayed sudden-onset panic and depression, and COVID-19 antibody laboratory testing.

scholarly journals The impact of chronic stress and eating types on active ghrelin levels in response to acute stress

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Christine Fahrngruber ◽  
Kalina Duszka ◽  
Jürgen König
Keyword(s):  
Chronic Stress ◽  
Eating Behavior ◽  
Social Stress ◽  
Acute Stress ◽  
Stress Test ◽  
Primary Objective ◽  
Trier Social Stress Test ◽  
Relaxation Techniques ◽  
Stress Exposure ◽  
The Impact

AbstractChronic stress is associated with impacting eating behavior, namely food choice and energy intake, with a shift towards more palatable and energy dense foods. Additionally, eating behavior is influenced by other psychological factors like mood and emotions. The categorization of people into eating types such as restrained, emotional, and external eaters has gained attraction. Reported changes in eating behavior due to psychological stress are only occasionally accompanied by measures of physiological hunger through ghrelin. The primary objective of this study was to investigate how chronic stress and acute cortisol reactivity affect active ghrelin secretion and how these outcomes account for different eating types. 16 healthy, young males (age: 23 ± 3 years, BMI: 22.5 ± 1.3kg/m2) with low (n = 8) and average-to-high (n = 8) chronic stress level were subjected to the Trier Social Stress Test (TSST) and a control version on two separate days. Active ghrelin, cortisol, glucose, and heart rate were measured throughout the test. Subjects rated their hunger by means of visual analog scale and current mood was assessed with the Positive and Negative Affect Scale (PANAS). In addition, participants filled out the Dutch Eating Behavior Questionnaire (DEBQ) to account for their subjective eating behavior. Overall ghrelin values where higher on the test day compared to the control day. Ghrelin values were also higher during the time leading up to the stress or control test (TSST) than during the conclusion of said tests. On both days, mean values for active ghrelin where higher in individuals with low chronic stress exposure compare to those with average-to-high chronic stress exposure. While values from test to control day decreased for lower stressed participants, they slightly increased for higher stressed participants. Cortisol responders displayed higher ghrelin values on test day than cortisol non-responders, but this association inverted for the control day. Results indicate that chronic stress influences acute stress response and further alters active ghrelin production, which in turn can influence eating behavior. Replication in a greater group of participants of differing weight and sex could yield a greater understanding of stress induced eating. Factors such as relaxation techniques and coping mechanisms could further improve our knowledge and evaluate treatment possibilities.

scholarly journals Noninvasive Brain Stimulation and Psychotherapy in Anxiety and Depressive Disorders: A Viewpoint

2019 ◽  
Vol 9 (4) ◽  
pp. 82 ◽  
Author(s):  
Moussa Chalah ◽  
Samar Ayache
Keyword(s):  
Brain Stimulation ◽  
Large Scale ◽  
Depressive Disorders ◽  
Behavioral Therapy ◽  
Neuropsychiatric Symptoms ◽  
Clinical Settings ◽  
Noninvasive Brain Stimulation ◽  
Psychotherapeutic Interventions ◽  
Sham Intervention ◽  
New Treatments

Among the most prevalent psychiatric conditions stand anxiety and depression. Psychotherapy and medications are considered effective treatments in these clinical settings. However, pharmacotherapy and psychotherapy (i.e., cognitive behavioral therapy (CBT)) administered in monotherapy or in a combined regimen do not result in satisfactory outcomes in all patients. Therefore, finding new treatments would be of great help. In the last three decades, noninvasive brain stimulation (NIBS) has emerged as a safe tool to improve several neuropsychiatric symptoms. The following work revisits the available reports that assessed the add-on value of NIBS techniques when combined to psychotherapy (CBT or related interventions) in mood and anxiety disorders. The available protocols targeted the prefrontal cortex, a region that was previously found to have an enhanced activity or functional connectivity after psychotherapeutic interventions. Promising yet scarce evidence exists on this matter. A discrepancy exists among the available reports regarding the type and duration of interventions, the patients’ clinical profiles, and the presence of a sham intervention. NIBS may have acted by enhancing psychotherapy effects on the top-down cognitive control of emotions. Combining both therapies may result in promising effects, but future large-scale trials are needed to judge the utility of this combination in psychiatric populations.

scholarly journals The effect of prescribed exercise volume on biomarkers of chronic stress in postmenopausal women: Results from the Breast Cancer and Exercise Trial in Alberta (BETA)

2019 ◽  
Vol 15 ◽  
pp. 100960 ◽  
Author(s):  
Christine M. Friedenreich ◽  
Qinggang Wang ◽  
Eileen Shaw ◽  
Emily V. Heer ◽  
Ruokun Zhou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Chronic Stress

Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

2016 ◽  
Vol 131 (2) ◽  
pp. 123-138 ◽  
Author(s):  
Veronica Begni ◽  
Marco Andrea Riva ◽  
Annamaria Cattaneo
Keyword(s):  
Synaptic Plasticity ◽  
Stress Response ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Brain Derived Neurotrophic Factor ◽  
Mitogen Activated Protein Kinase ◽  
Bdnf Expression ◽  
Pathological Conditions ◽  
Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

scholarly journals Telomere Shortening in Formerly Abused and Never Abused Women

2011 ◽  
Vol 14 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Janice Humphreys ◽  
Elissa S. Epel ◽  
Bruce A. Cooper ◽  
Jue Lin ◽  
Elizabeth H. Blackburn ◽  
...  
Keyword(s):  
Telomere Length ◽  
Chronic Stress ◽  
Partner Violence ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Cellular Aging ◽  
Abused Women ◽  
Peripheral Blood Mononuclear ◽  
Convenience Sample

Recent studies suggest that chronic psychological stress may accelerate aging at the cellular level. Telomeres are protective components that stabilize the ends of chromosomes and modulate cellular aging. Women exposed to intimate partner violence (IPV) experience chronic stress and report worse health. The purpose of this exploratory study was to examine telomeric DNA length in women who have experienced chronic stress related to IPV. We hypothesized that IPV exposure would be associated with shorter telomere length. The investigation used a cross-sectional design to study telomere length in women with a history of IPV exposure and control women who reported no prior exposure to IPV. Advertisements and public notices were used to recruit a convenience sample of healthy women. Mean leukocyte telomere length was measured in DNA samples from peripheral blood mononuclear cells (PBMCs) by a quantitative polymerase chain reaction assay (qPCR). Telomere length was significantly shorter in the 61 formerly abused women compared to the 41 controls ( t = 2.4, p = .02). Length of time in the abusive relationship and having children were associated with telomere length after controlling for age and body mass index (BMI) ( F(2, 99) = 10.23, p < .001). Numerous studies suggest that women who experience IPV have poorer overall health. It is often presumed that the stress of IPV may be causing greater morbidity. Findings from this descriptive study suggest a link between IPV exposure, duration of IPV-related stress, and telomere length molecular mechanisms that regulate cellular aging.

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