Negative Effects Of Chronic Stress Research Articles

Formation of resilience of student youth by physical therapy methods

The article examines the negative impact of chronic stress caused by military aggression on the state of mental health of students, which directly affects their desire and ability to study effectively. The purpose of the work: to systematize the negative effects of chronic stress on the health of young people and to outline approaches to the formation of students' resilience using physical therapy methods. Scientific novelty: the main factor in preserving the health of students is an effectively organized pedagogical process and the correct use of pedagogical technologies. Methods of combating stress consist in removing emotional tension and changing a person's psychological mood. Students need to be taught how to manage stress and recover from exhaustion. The Kessler Psychological Distress Scale (K10), a "stress thermometer", and the subjective units of distress scale (SUDS) are used to monitor the impact of stress on the psycho-emotional state. Physical stress management methods include: regular physical activity, deep breathing, massage, reflexology, progressive muscle relaxation, healthy eating, sleep and rest.
 Conclusions: 1. The priority of higher education institutions of Ukraine should be the formation of resilience of all participants in the educational process. 2. Since during the war it is impossible to eliminate the source of stress, it is necessary to know its signs and manage it with stress management methods (regular physical activity, healthy diet, relaxation techniques, time planning, making positive changes in life). 3. Prevention of the negative impact of chronic stress on students, the search for resources to restore their physical and mental health, with the help of stress management and physical therapy methods, is a promising direction of scientific research.

Efficient Feature-Selection-Based Stacking Model for Stress Detection Based on Chest Electrodermal Activity.

Contemporary advancements in wearable equipment have generated interest in continuously observing stress utilizing various physiological indicators. Early stress detection can improve healthcare by lessening the negative effects of chronic stress. Machine learning (ML) methodologies have been modified for healthcare equipment to monitor user health situations utilizing sufficient user information. Nevertheless, more data are needed to make applying Artificial Intelligence (AI) methodologies in the medical field easier. This research aimed to detect stress using a stacking model based on machine learning algorithms using chest-based features from the Wearable Stress and Affect Detection (WESAD) dataset. We converted this natural dataset into a convenient format for the suggested model by performing data visualization and preprocessing using the RESP feature and feature analysis using the Z-score, SelectKBest feature, the Synthetic Minority Over-Sampling Technique (SMOTE), and normalization. The efficiency of the proposed model was estimated regarding accuracy, precision, recall, and F1-score. The experimental outcome illustrated the efficacy of the proposed stacking technique, achieving 0.99% accuracy. The results revealed that the proposed stacking methodology performed better than traditional methodologies and previous studies.

Beliefs about stress moderate the association between COVID-19-related work demands and burnout symptoms in physicians.

The present study set out to investigate the role of different stress beliefs (positive and negative beliefs about stress, as well as perceived control) on the association between central COVID-19-related work demands and burnout symptoms in physicians during the second lockdown of the SARS-CoV-2 pandemic. N=154 practicing physicians (mean [SD] age=37.21 [9.43] years]; 57.14% female) participated in our cross-sectional German-wide online survey and answered questions about sociodemographic factors, their current work situation, their stress beliefs, and their current burnout symptoms. Moderation analyses revealed significant interaction effects between stress beliefs and specific COVID-19-related work demands on the prediction of burnout symptoms, most consistent with respect to perceived control. Positive believes about stress and its controllability were cross-sectional associated with reduced, negative believes about stress however with enhanced associations between COVID-19-related work demands and burnout symptoms. This finding indicates, if confirmed by longitudinal research, the potential of the usage of stress beliefs in prevention programs for physicians in order to mitigating negative effects of chronic stress.

Nutrition in conditions of martial law: anti-stress diet

Introduction. In extreme conditions of martial law, a person’s life is under constant threat, which leads to chronic stress, reduces the activity of the immune system and contributes to the development of chronic diseases and depression. Problem. Taking into account the complexity of the martial law in Ukraine, it is extremely important to provide the population with sufficient and balanced nutrition necessary to preserve the life and health of citizens, as well as possible alimentary prevention of the negative effects of chronic stress. Methods. Theoretical methods are used to reveal the essence of the problem and determine the directions of its solution. The principles of nutrition of people with high psycho-emotional loads became the basis for the development of recommendations for anti-stress diet. Results. Negative factors of influence and consequences of metabolic disorders in the human body under the influence of chronic stress have been studied. The expediency of using the principles of detoxification nutrition against the background of nutritional support of the cardiovascular, nervous, immune and digestive systems of the human body has been established. Approximate anti-stress diet is recommended for persons with high psycho-emotional stress. Conclusions. The information of sources is summarized, in which scientifically substantiated approaches and directions of alimentary correction of metabolic disorders caused by chronic stress and their consequences for the human body are proposed. The possible ways of correcting the nutrition of the population in martial law are scientifically substantiated and the approximate anti-stress diet of health nutrition for people in martial law is recommended.

A Long-Term Energy-Rich Diet Increases Prefrontal BDNF in Sprague-Dawley Rats.

Findings of the effect of high-fat feeding including “Cafeteria Diets” (CAF) on brain-derived neurotrophic factor (BDNF) in the hippocampus (HIP) and prefrontal cortex (PFC) in rodents are conflicting. CAF is a non-standardized, highly palatable energy-rich diet composed by everyday food items for human consumption and is known to induce metabolic syndrome and obesity in rats. However, the highly palatable nature of CAF may counteract a negative effect of chronic stress on anticipatory behavior and synaptic plasticity in the hippocampus, hence represent a confounding factor (e.g., when evaluating functional effects on the brain). This study investigated the effects of a chronic, restricted access to CAF on BDNF, monoamine neurotransmitters, and redox imbalance in HIP and PFC in male rats. Our results show that CAF induced BDNF and its receptor TrkB in PFC compared to the controls (p < 0.0005). No differences in monoamine neurotransmitters were detected in either PFC or HIP. CAF increased dehydroascorbic acid and decreased malondialdehyde in PFC (p < 0.05), suggesting an early redox imbalance insufficient to induce lipid peroxidation. This study supports that a chronic CAF on a restricted schedule increases BDNF levels in the PFC of rats, highlighting that this may be a suboptimal feeding regime when investigating the effects of diet-induced obesity in the brain and emphasizing this as a point of attention when comparing the findings.

Training level reveals a dynamic dialogue between stress and memory systems in birds

Chronic stress profoundly affects forms of declarative memory, such as spatial memory, while it may spare non-declarative memory, such as cue-based memory. It is known, however, that the effects of chronic stress on memory systems may vary according to the level of training of an individual was submitted. Here, we investigated, in birds, how chronic stress impact spatial and cue-based memories according to training level. For that, control and chronically stressed Japanese quail were trained in a task that could be solved using spatial and cue-based memory and tested for their memory performance after 5 and 15 training days (initial training and overtraining, respectively) and following an emotional challenge (exposure to an open field). Our results showed that, compared to control quail, chronic stress impacted negatively spatial memory performances in stressed birds after initial training, but these differences were lowered after overtraining. Control birds seemed to shift from spatial to cue-based memory to solve the task across overtraining. However, an emotional challenge before testing reinstated the negative impact of chronic stress on spatial memory performances between the groups, revealing that chronic stress/overtraining did not eliminate the spatial memory and differences caused by stressors can reemerge depending on the individual’s immediate psychological state. Contrary to spatial memory, cue-based memory was not affected in chronically stressed birds compared to control birds in any test occasion, confirming its resistance against the negative effects of chronic stress. Altogether these findings reveal a dynamic dialogue between stress, training level, and memory systems in birds.

Spiritual Fitness: A New Dimension in Alzheimer's Disease Prevention.

Background:Religious and spiritual interventions may have an effect on Alzheimer’s disease prevention. Kirtan Kriya meditation has been shown to mitigate the deleterious effects of chronic stress on cognition, reverse memory loss, and create psychological and spiritual wellbeing, which may reduce multiple drivers of Alzheimer’s disease risk.Objective:To detail a new concept in medicine called Spiritual Fitness, a merging of stress reduction, basic wellbeing, and psycho/spiritual wellbeing to prevent Alzheimer’s disease.Methods:The literature on the topics mentioned above is described, including an in-depth discussion on why and how each are critical to advancing the future of Alzheimer’s disease prevention. The many negative effects of chronic stress, and the benefits of Kirtan Kriya, are reviewed. The four pillars of basic wellbeing, six practical aspects of psychological wellbeing, and the four new non-sectarian features of spiritual fitness are then disclosed. Moreover, instructions on practicing Kirtan Kriya are offered in the Supplementary Material.Conclusion:Religious and spiritual practices, including Kirtan Kriya, are crucial components in the development of enhanced cognition and well-being, which may help prevent and, in some cases, reverse cognitive decline. The key point of this review is that making a commitment to live a brain longevity lifestyle including spiritual fitness is a critically important way for aging Alzheimer’s disease free. We hope that this article will inspire scientists, clinicians, and patients to embrace this new concept of spiritual fitness and make it a part of every multidomain program for the prevention of cognitive disability.

More than a Trait: Longitudinal Changes in Psychological Resilience, Mood and Cognition in Late Life Major Depression

<h3>Introduction</h3> Major depressive disorder in older adults or late-life major depression (LLMD) often responds poorly to antidepressants and increases risks of morbidity, mortality, and dementia. Psychological resilience, or the ability to quickly return to a pre-stimulus state after a stressful event, is an understudied construct with potential clinical implications for LLMD. Higher baseline resilience is associated with LLMD remission. While resilience is often treated as a trait, it is better conceptualized as a dynamic pattern of adaptation that can change over time. Little is known regarding possible changes in resilience that accompany LLMD. The impact of resilience on cognitive functioning in LLMD is also unclear. Resilience may prevent cognitive decline by attenuating the negative effects of chronic stress or greater cognitive control may augment an individual's resilience. Our aim within the following study is to observe whether long-term changes in resilience occur in LLMD. Secondly, if changes in resilience are observed to be present, we sought to determine if these changes correlate with changes in cognition and mood over a two year period. <h3>Methods</h3> All subjects (n = 123) were enrolled in NBOLD, an IRB approved, NIMH R01 funded study at UConn Health. All subjects provided informed consent to participate. All subjects met criteria for major depression as established by a geriatric psychiatrist. The Montgomery-Asberg Depression Rating Scale (MADRS) was used to measure depression severity. Each subject completed several self-report measures, including the Brief Resilience Scale (BRS). Participants also underwent neuropsychological evaluations to assess cognition. Assessments were repeated at 12 and 24 months post-enrollment. This was a naturalistic observation study; all participants were offered open-label treatment with sertraline at study onset, but could have been maintained on another antidepressant, or elected not to undergo treatment. Statistical analysis: Demographic differences were compared between individuals above and below the median BRS score. Linear regressions were used to assess the relationship between changes in BRS score, MADRS, and cognitive variables due to the availability of repeated measures. <h3>Results</h3> The median baseline BRS score was 17 (IQR: 13 – 20). Individuals with low resilience (less than median BRS) were more likely to be female (66%, n=40) vs high resilience (28.6% female, n = 18, p <0.001). Low resilience individuals also have a higher baseline MADRS score (mean = 22.1, SD = 5.3) vs high resilience individuals (mean = 17.1, SD = 6.3, p <0.001). Over the two year period, many patient's resilience scores increased (43.5%, n = 54), while other patients' scores didn't change (37%, n = 46) or decreased (19.3%, n = 24). On average, resilience increased by a mean of 1.72 points (SD = 4.4, p = 0.003). BRS increased the most between treatment start (mean = 16.7, SD = 4.72) and 12 months (mean = 18.33, SD = 5.0, p <0.001). With linear regression, increased BRS from baseline to 12 months was associated with lower MADRS score at 24 months (β(SE) = -0.36(0.16), p = 0.03) after adjusting for confounders (including baseline MADRS). BRS score change from baseline to 24 months was not associated with lower MADRS score at 24 months (β(SE) = -0.1(0.15), p = 0.5). For cognition, higher baseline resilience was associated with decreased change in Logical Memory II score at 24 months (β(SE)= -0.27(0.12), p = 0.02). <h3>Conclusions</h3> Resilience is shown to be a dynamic process variable that changes during LLMD treatment. We also demonstrated that shorter term changes in resilience (first 12 months of treatment) are more strongly associated with MADRS score at two years as compared to changes in resilience during the entire treatment period. These "early resilience responders" to treatment may represent a unique subpopulation particularly well-matched to antidepressant therapy. While increases in resilience are a predictor of decreased MADRS at 24 months, we report that higher <i>baseline</i> resilience correlated to decreased cognitive gains on the LMII. This might be due to near-ceiling effects on cognitive tests in high resilient individuals. Future directions include assessing the value of resilience therapy. Prior studies have demonstrated that resilience can be increased with meditation and behavioral therapy. These modalities could guide new therapeutic techniques for individuals with LLMD. <h3>Funding</h3> Funding is provided by the National Institute of Mental Health–funded R01 grant entitled, "Neurobiology and Adverse Outcomes of Neuroticism in Late-life Depression" (MH096725)

Protectoral action of molsidomin ATP combination in chronic stress in young and old rats

Adaptive reactions to chronic stress, reaching a certain intensity, can become harmful and be involved in any pathological process. Therefore, the search for new ways to increase the adaptive capacity reduced with age and the body's resistance to the negative effects of chronic stress remains relevant. The aim of the study was to experimentally study the age-related protective properties of the combination of molsidomine and ATP in chronic mild stress. The experiments were performed on young (6 months) and old (26 months) Wistar rats exposed to stressors that changed periodically at random for 8 weeks. During the 6-8th week of the experiment, against the background of stress, the animals were sublingually administered a pharmacological combination based on molsidomine - 2 mg / kg, ATP - 10 mg / kg. It was found that the adaptive reactions of young and old animals to chronic stress have qualitative and quantitative differences. Chronic stress in old rats caused changes in behavior and psycho-emotional state, deterioration of cognitive function, changes in lipoperoxidation. On the part of the immune system in old rats, against the background of a pronounced age involution of lymphoid organs, no significant changes in thymus mass and cellularity were observed during chronic stress, while the mass and cellularity of the spleen increased. The combination of molsidomine and ATP prevented post-stress changes in animal behavior, reduced anxiety, normalized social activity, restored the lost ability to recognize, improved cognitive function. The drug contributed to the preservation of the function of immunocompetent organs in young animals and to a lesser extent showed a protective effect in older animals against the background of involutional changes caused by both aging and chronic stress. The combination of molsidomine and ATP had an antioxidant effect. Thus, in chronic mild stress, older animals showed a different response from young animals to both stress and the administration of molsidomine with ATP. The applied pharmacological combination can be considered as a promising stress-protective agent that has a complex effect on various pathogenetic links of chronic stress due to its neuro- and immunomodulatory, energy-saving, antioxidant properties. Keywords: aging, chronic stress, anxiety, social activity, cellularity of the thymus and spleen, lipid peroxidation, combination of molsidomine and ATP, pharmacological action.

Chronic stress promotes EMT-mediated metastasis through activation of STAT3 signaling pathway by miR-337-3p in breast cancer

Chronic stress could induce cancer metastasis by constant activation of the sympathetic nervous system, while cellular mechanism remains obscure. The aim of this research is to explore the metastasis associated negative effect of chronic stress. The analysis of transcriptome sequencing implied that activation of STAT3 signaling pathway by downregulated miR-337-3p might be a potential mechanism to induce epithelial to mesenchymal transition (EMT) of cancer cell and promote metastasis under chronic stress. We also verified this biological process in further experiments. Downregulation of miR-337-3p could downregulate E-cadherin expression and upregulate vimentin expression in vitro and in vivo. STAT3, related signal pathways of which are involved in metastasis regulation, was directly targeted by miR-337-3p. In conclusion, the above results denoted that activation of miR-337-3p/STAT3 axis might be a potential pathway for the increasing metastasis of breast cancer under chronic stress.

Reducing Allostatic Load in Depression and Anxiety Disorders: Physical Activity and Yoga Practice as Add-On Therapies.

The allostatic load (AL) index constitutes a useful tool to objectively assess the biological aspects of chronic stress in clinical practice. AL index has been positively correlated with cumulative chronic stress (physical and psychosocial stressors) and with a high risk to develop pathological conditions (e.g., metabolic syndrome, cardiovascular pathology, inflammatory disorders) and the so-called stress-related psychiatric disorders, including anxiety and depressive disorders. Chronic stress has negative effects on brain neuroplasticity, especially on hippocampal neurogenesis and these effects may be reversed by antidepressant treatments. Several evidences indicate that non-pharmacological interventions based on physical activity and yoga practice may add synergizing benefits to classical treatments (antidepressant and benzodiazepines) for depression and anxiety, reducing the negative effects of chronic stress. The aim of this review is to provide a general overview of current knowledge on AL and chronic stress in relation to depression and anxiety, physical activity and yoga practice.

The effects of stress on cardiovascular disease and Alzheimer's disease: Physical exercise as a counteract measure.

AD is a complicated multi-systemic neurological disorder that involves different biological pathways. Several risk factors have been identified, including chronic stress. Chronic stress produces an alteration in the activity of the hypothalamic pituitary adrenal (HPA) system, and the autonomic nervous system (ANS), which over time increase the risk of AD and also the incidence of cardiovascular disease (CVD) and risk factors, such as hypertension, obesity and type 2 diabetes, associated with cognitive impairment and AD. Considering the multi-factorial etiology of AD, understanding the complex interrelationships between different risk factors is of potential interest for designing adequate strategies for preventing, delaying the onset or slowing down the progression of this devastating disease. Thus, in this review we will explore the general mechanisms and evidence linking stress, cardiovascular disease and AD, and discuss the potential benefits of physical activity for AD by counteracting the negative effects of chronic stress, CVD and risk factors.

Oxidative stress, inflammatory reactions and apoptosis mediated the negative effect of chronic stress induced by maternal separation on the reproductive system in male mice

Exposure to severe and long-lasting stressors during early postnatal life negatively affects development of the brain and associated biological networks. Maternal separation (MS) is a valid stressful experience in early life that adversely affects neurobiological circuits. In the present study, we aimed to evaluate the effects of MS on sperm quality and histology of the testis in adult male mice. In this study, male mice were subjected to MS during post-natal days (PND) 2–14. Sperm parameters, histological alterations in the testicular tissue, ROS production (using DCFH-DA assay), gene expression of TLR4, NLRP3, TNFα, BAX, ASC, caspase-1 and BCL-2 (using RT-PCR), protein levels of caspase-3 and caspase-8 (using western blotting), and protein levels of IL-1β, IL-18, GPx and ATP (using ELISA) as well as protein expression of caspase-1 and NLRP3 (using immunocytochemistry) were evaluated. Findings showed that MS decreased count, morphology and viability of spermatozoa. MS decreased the diameter of seminiferous tubules and decreased the thickness of seminiferous epithelium. Furthermore, MS increased the level of ROS production and decreased the concentrations of GPx and ATP. MS led to increased expression of TLR4, NlRP3, TNFα, caspase-1, ASC, IL-1β and IL-18. In addition, MS induced apoptosis as evidenced by increased BAX, caspase-3 and caspase-8 as well as decreased BCL-2 expression. We concluded that early life stress induced by MS has detrimental effects on sperm parameters and testicular tissue. Our results suggest that these effects are mediated by activation of ROS production, and alterations in mitochondrial function, inflammatory processes and apoptosis pathways.

Manipulation of Ambient Housing Temperature To Study the Impact of Chronic Stress on Immunity and Cancer in Mice.

Mice are the preeminent research organism in which to model human diseases and study the involvement of the immune response. Rapidly accumulating evidence indicates a significant involvement of stress hormones in cancer progression, resistance to therapies, and suppression of immune responses. As a result, there has been a concerted effort to model human stress in mice. In this article, we discuss recent literature showing how mice in research facilities are chronically stressed at baseline because of environmental factors. Focusing on housing temperature, we suggest that the stress of cool housing temperatures contributes to the impact of other imposed experimental stressors and therefore has a confounding effect on mouse stress models. Furthermore, we propose that manipulation of housing temperature is a useful approach for studying the impact of chronic stress on disease and the immune response and for testing therapeutic methods of reducing the negative effects of chronic stress.

Effect of Restraint Stress on Plasma PTH Concentration and Its Molecular Targets Expressions in Wistar Rats.

BackgroundThere are limited numbers of experimental studies related to the potential role of parathormone/parathyroid hormone (PTH) in response to psychological stress. In the current study, we aimed to cross-examine, for the first time, changes in PTH plasma concentration and the expression of its molecular targets mediated by restraint stress in rats.MethodsMale Wistar rats (n = 42) were separated into control and stressed groups. They were further divided into two groups that received chronic restraint stress (CRS) for 7 and 28 consecutive days (n = 7 for each group). Elevated plus maze and tail suspension test were used to determine the anxiety- and depressive-like behaviors of a different set of rats including stress and control groups (n = 7 for each group). The plasma levels of adrenocorticotropic hormone (ACTH), corticosterone, and intact parathormone (iPTH) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, alterations in the expressions of glucocorticoid receptor (GR), calcium sensing receptor (CaSR), and parathormone receptor (PTHR1) of kidney and total thyroid gland tissues were estimated by Western Blotting.ResultsThere was no significant difference in the plasma level of iPTH while significant increases in the levels of ACTH and corticosterone were noted in the stressed-animals at day 7 and 21 (P = 0.010 and P = 0.016, respectively) of restraint stress. However, we found a negative correlation between iPTH and corticosterone levels in acute restraint stress (r = 0.771, P = 0.002). In addition, the expression of PTHR1 significantly decreased in the kidney at day 7 (P = 0.001) and in the thyroid gland at day 28 (P = 0.05) in response to CRS.ConclusionsTo sum up, CRS has a significant effect on the expression of parathormone receptor rather than the iPTH concentration. The present results add a new dimension to stress research through the negative effect of chronic stress on the PTH signaling pathway.

Contact to Nature Benefits Health: Mixed Effectiveness of Different Mechanisms.

How can urban nature contribute to the reduction of chronic stress? We twice measured the concentration of the “stress hormone” cortisol in the hair of 85 volunteer gardeners (six months apart), relating cortisol level change to (self-reported) characteristics of their recreational activities. Both time spent in nature and physical activity led to decreases in cortisol, while time spent being idle led to an increase. At high levels of present stressors, however, the relationship for time spent in nature and for idleness was reversed. Time spent with social interaction had no effect on cortisol levels. Our results indicate that physical activity is an effective means of mitigating the negative effects of chronic stress. The results regarding the time spent in nature and time spent being idle are less conclusive, suggesting the need for more research. We conclude that if chronic stress cannot be abolished by eradicating its sources, public health may take to measures to reduce it—providing urban nature being one effective possibility.

Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke

How stress influences brain repair is an issue of considerable importance, as patients recovering from stroke are known to experience high and often unremitting levels of stress post-event. In the current study, we investigated how chronic stress modified the key cellular components of the neurovascular unit. Using an experimental model of focal cortical ischemia in male C57BL/6 mice, we examined how exposure to a persistently aversive environment, induced by the application of chronic restraint stress, altered the cortical remodeling post-stroke. We focused on systematically investigating changes in the key components of the neurovascular unit (i.e. neurons, microglia, astrocytes, and blood vessels) within the peri-infarct territories using both immunohistochemistry and Western blotting. The results from our study indicated that exposure to chronic stress exerted a significant suppressive effect on each of the key cellular components involved in neurovascular remodeling. Co-incident with these cellular changes, we observed that chronic stress was associated with an exacerbation of motor impairment 42 days post-event. Collectively, these results highlight the vulnerability of the peri-infarct neurovascular unit to the negative effects of chronic stress.

Reconsidering the role of glial cells in chronic stress-induced dopaminergic neurons loss within the substantia nigra? Friend or foe?

Exposure to psychological stress is known to seriously disrupt the operation of the substantia nigra (SN) and may in fact initiate the loss of dopaminergic neurons within the SN. In this study, we aimed to investigate how chronic stress modified the SN in adult male mice. Using a paradigm of repeated restraint stress (an average of 20h per week for 6weeks), we examined changes within the SN using western blotting and immunohistochemistry. We demonstrated that chronic stress was associated with a clear loss of dopaminergic neurons within the SN. The loss of dopaminergic neurons was accompanied by higher levels of oxidative stress damage, indexed by levels of protein carbonylation and strong suppression of both microglial and astrocytic responses. In addition, we demonstrated for the first time, that chronic stress alone enhanced the aggregation of α-synuclein into the insoluble protein fraction. These results indicate that chronic stress triggered loss of dopaminergic neurons by increasing oxidative stress, suppressing glial neuroprotective functions and enhancing the aggregation of the neurotoxic protein, α-synuclein. Collectively, these results reinforce the negative effects of chronic stress on the viability of dopaminergic cells within the SN.

KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID-ACTING ANTIDEPRESSANTS.

Major depressive disorder (MDD) is a common and debilitating psychiatric disorder. Traditional antidepressants are of limited efficacy and take weeks to months to yield full therapeutic effects. Thus, there is a clear need for effective rapid-acting antidepressant medications. The N-methyl-d-aspartate receptor (NMDA-R) antagonist, ketamine, has received a great deal of attention over the last 20 years due to the discovery that a single subanesthetic dose leads to a rapid antidepressant effect in individuals with treatment-resistant depression. Animal and human research suggest that ketamine's antidepressant effects are mediated by a glutamate surge that leads to a cascade of events that result in synaptogenesis and reversal of the negative effects of chronic stress and depression, particularly within the prefrontal cortex (PFC). Preclinical and clinical data have provided compelling insights into the mechanisms underlying the rapid-acting antidepressant effects of ketamine. This review discusses stress-related neurobiology of depression and the safety, tolerability, and efficacy of ketamine for MDD, along with a review of ketamine's mechanism of action and prospective predictors of treatment response. Research limitations and future clinical prospects are also discussed.

Angiotensin II type 1 receptor blockade diminishes negative effect of chronic stress on memory via upregulation of brain-derived neurotrophic factor

IntroductionA critical need exists for progress in the characterization of targets for pro-cognitive drug discovery. We previously demonstrated that Telmisartan (TLM), an angiotensin type 1 receptor (AT1) blocker and partial agonist of peroxisome proliferator-activated receptor gamma (PPARγ), alleviates cognitive decline in chronically stressed rats. Understanding of mechanistic background of this phenomenon is hampered by both dual binding sites of TLM and limited data on the molecular consequences of central AT1 blockade and PPARγ activation.ObjectivesTo discriminate molecular effects of AT1 blockade and PPARγ activation in stress induced memory impairment.AimsIn this study, we investigated mechanism of neuroprotection provided by TLM in chronic psychological stress.MethodsWe analyzed BDNF gene expression in the hippocampus (HIP) and medial prefrontal cortex (mPFC) in chronically restrained stressed Wistar rats (2.5 h, 21 days), repeatedly treated with TLM (1 mg/kg), GW9662 (0.5 mg/kg) – a selective PPARγ receptor antagonist, or both in combination. TATA box binding protein (Tbp) was an internal control for expression studies.ResultsAlterations of mRNA expression of BDNF are shown on Figs. 1 and 2.ConclusionsAT1 receptor blockade restores cognitive functions in chronically stressed subjects, which is associated with changes in primarily cortical gene expression.Disclosure of interestThe authors have not supplied their declaration of competing interest.