Neuroimmune Interactions in Stress and Depression: Exploring the Molecular and Cellular Mechanisms within the Neuroinflammation-depression Nexus.

BACKGROUND: The escalating global burden of stress and depression underscores an urgent need to unravel their complex interrelationships and underlying mechanisms. This investigation delves into the intricate dynamics between stress and depression, spotlighting the Neuroimmunoinflammatory Stress Model (NIIS), which elucidates the pivotal role of cellular and molecular pathways in mediating these conditions. METHODS: Through an exhaustive review of literature spanning epidemiology, neurobiology, and psychoneuroimmunology, this study synthesizes the current understanding of stress and depression. It accentuates the definitional scopes, interplay, and intricacies of the NIIS model, which integrates neuroimmune-inflammatory responses into the conceptual framework of the stress-depression interaction. RESULTS: By identifying stress as a multifactorial reaction to perceived adversities and depression as a manifestation of prolonged stress exposure, our analysis foregrounds the NIIS model. This paradigmatic model reveals the transition from normal stress responses to pathological neuroinflammatory pathways, highlighting neurotransmitter imbalances, disruptions in neuronal and glial homeostasis, and ensuing low-grade neuroinflammation as key factors in the pathogenesis of depression under chronic stress conditions. The NIIS model identifies prolonged cellular pro-inflammatory stress of neurons and microglia as a fundamental pathological subsystem of many neuropsychiatric disorders. In turn, neuroinflammation and associated neurodegenerative processes are complications of chronic psychoemotional stress, which can clinically manifest as depression. CONCLUSIONS: The NIIS model views depression as the terminal stage of chronic stress, pathogenetically linked to latent neuroinflammation. This insight not only advances our understanding of their etiopathogenesis but also paves the way for developing precise therapeutic interventions.

Computational Analysis of CD46 Protein Interaction with SARS-CoV-2 Structural Proteins: Elucidating a Putative Viral Entry Mechanism into Human Cells.

This study examines an unexplored aspect of SARS-CoV-2 entry into host cells, which is widely understood to occur via the viral spike (S) protein's interaction with human ACE2-associated proteins. While vaccines and inhibitors targeting this mechanism are in use, they may not offer complete protection against reinfection. Hence, we investigate putative receptors and their cofactors. Specifically, we propose CD46, a human membrane cofactor protein, as a potential putative receptor and explore its role in cellular invasion, acting possibly as a cofactor with other viral structural proteins. Employing computational techniques, we created full-size 3D models of human CD46 and four key SARS-CoV-2 structural proteins-EP, MP, NP, and SP. We further developed 3D models of CD46 complexes interacting with these proteins. The primary aim is to pinpoint the likely interaction domains between CD46 and these structural proteins to facilitate the identification of molecules that can block these interactions, thus offering a foundation for novel pharmacological treatments for SARS-CoV-2 infection.

JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.

The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological and pathological processes such as inflammation and stress. Dysregulation in this pathway can lead to severe immunodeficiencies and malignancies, and its role extends to neurotransduction and pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological and inflammatory disorders, their application has generally been limited to diseases with similar pathogenic features. Despite the modest expression of JAK-STAT in the CNS, it is crucial for functions in the cortex, hippocampus, and cerebellum, making it relevant in conditions like Parkinson's disease and other neuroinflammatory disorders. Furthermore, the influence of the pathway on serotonin receptors and phospholipase C has implications for stress and mood disorders. This review expands the understanding of JAK-STAT, moving beyond traditional immunological contexts to explore its role in stress-related disorders and CNS function. Recent findings, such as the effectiveness of Jakinibs in chronic conditions such as rheumatoid arthritis, expand their therapeutic applicability. Advances in isoform-specific inhibitors, including filgotinib and upadacitinib, promise greater specificity with fewer off-target effects. Combination therapies, involving Jakinibs and monoclonal antibodies, aiming to enhance therapeutic specificity and efficacy also give great hope. Overall, this review bridges the gap between basic science and clinical application, elucidating the complex influence of the JAK-STAT pathway on human health and guiding future interventions.

Early-life maternal deprivation in rats increases sensitivity to the subsequent stressors: a pilot study.

Early life experiences, particularly maternal deprivation (MD), have long-lasting implications on emotional and cognitive development. Using Wistar rats as a model, this study explores the impact of MD followed by predator stress exposure (PSS) to simulate aspects of post-traumatic stress disorder (PTSD). A cohort of 41 male rat pups underwent MD from postnatal days 2 to 14, followed by PSS at day 90. Female rat pups were not included in the experiment. Behavior was subsequently assessed using the Elevated Plus Maze test 14 days post-PSS. While MD led to subtle changes such as decreased activity and increased anxiety-like behavior, PSS induced pronounced anxiogenic effects. Notably, PSS after MD resulted in decreased basal corticosterone levels, mirroring conditions observed in PTSD. The findings suggest that although MD itself does not induce significant behavioral changes, it predisposes individuals to heightened sensitivity to subsequent stressors. This study underscores the utility of a two-stage PSS model for more accurately reflecting the complexities inherent in stress-related disorders, including PTSD.

Somatic and psychological distress among Russian university students during the COVID-19 pandemic.

OBJECTIVE: Previous studies highlighted a high prevalence of mental health issues among students during the COVID-19 pandemic, but there is no evidence from Russia. This study was aimed to examine the prevalence of somatic and psychological distress among Russian university students. METHOD: The cross-sectional study was conducted in March-April 2021. The participants were university students from several regions of Russia (N = 1236). The Patient Health Questionnaire-15 and Depression, Anxiety, and Stress Scales-21 were used to measure the somatic and psychological distress. RESULTS: The prevalence of somatic burden, depression, anxiety, and stress was 72.2%, 54.7%, 63.4%, and 55.4%, respectively. Somatic burden, anxiety, and stress were more frequently observed in females and students with experience of COVID-19 disease compared to males and students without experience of COVID-19 disease. CONCLUSIONS: These data illuminate the high prevalence and potential risk factors for somatic and psychological distress among Russian university students and determine the importance of psychoeducation and preventive measures in the Russian university environment.

Big Five Traits as Predictors of a Healthy Lifestyle during the COVID-19 Pandemic: Results of a Russian Cross-Sectional Study.

The healthy lifestyle of people around the world has changed dramatically during the COVID-19 pandemic. The personality risk factors for these processes from around the world remain understudied. This study aimed to examine the associations of the Big Five traits with a healthy lifestyle during the COVID-19 pandemic. In a cross-sectional study, data from 1215 Russian university students were analyzed. Participants completed the Big Five Inventory-10 and Short Multidimensional Inventory Lifestyle Evaluation. The results showed that personality traits predicted many dimensions of a healthy lifestyle during the COVID-19 pandemic. Diet and nutrition were positively predicted by extraversion, agreeableness, and conscientiousness, and it was negatively predicted by neuroticism. Substance abuse was positively predicted by agreeableness and conscientiousness, and it was negatively predicted by extraversion. Physical activity was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Stress management was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Restorative sleep was positively predicted by extraversion and conscientiousness, and it was negatively predicted by neuroticism. Social support for healthy practices was positively predicted by extraversion, agreeableness, and conscientiousness. Environmental exposures were positively predicted by extraversion, and neuroticism was positively and negatively predicted by conscientiousness. Our findings may be useful for further exploration of personality risk factors for healthy practices in challenging life circumstances.

Exposure to chronic stressor upsurges the excitability of serotoninergic neurons and diminishes concentrations of circulating corticosteroids in rats two weeks thereafter.

BACKGROUND: Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. Under stress conditions, the brain serotoninergic (5-HT) system plays an important role. METHODS: We tested the hypothesis that repeated PS exposure alters the excitability of 5-HT neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawley rats were exposed to PS for 10 min daily for 10 consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. RESULTS: Measurements by in vivo electrophysiology showed increased firing activity of 5-HT neurons in rats exposed to PS. Exposure to PS resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands and the relative weight of the adrenals were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. PS exposure failed to induce changes in the gene expression of selected adrenal steroidogenic factors. CONCLUSION: Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats who experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.

A Rat Model of Post-Traumatic Stress Syndrome Causes Phenotype-Associated Morphological Changes and Hypofunction of the Adrenal Gland.

BACKGROUND: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production. METHODS: Rats were exposed to PSS for ten days. Thirty days later, the rats' anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex. RESULTS: Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the zona fasciculata and an increase in the thickness of the zona intermedia. The increase in the thickness of the zona intermedia was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the zona fasciculata of high-anxiety rats was significantly smaller than that of control or low-anxiety rats. CONCLUSION: Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder.

Cardiac injury in rats with experimental posttraumatic stress disorder and mechanisms of its limitation in experimental posttraumatic stress disorder-resistant rats.

Traumatic stress causes posttraumatic stress disorder (PTSD). PTSD is associated with cardiovascular diseases and risk of sudden cardiac death in some subjects. We compared effects of predator stress (PS, cat urine scent, 10 days) on mechanisms of cardiac injury and protection in experimental PTSD-vulnerable (PTSD) and -resistant (PTSDr) rats. Fourteen days post-stress, rats were evaluated with an elevated plus-maze test, and assigned to PTSD and PTSDr groups according to an anxiety index calculated from the test results. Cardiac injury was evaluated by: 1) exercise tolerance; 2) ECG; 3) myocardial histomorphology; 4) oxidative stress; 5) pro- and anti-inflammatory cytokines. Myocardial heat shock protein 70 (HSP70) was also measured. Experimental PTSD developed in 40% of rats exposed to PS. Exercise tolerance of PTSD rats was 25% less than control rats and 21% less than PTSDr rats. ECG QRS, QT, and OTc intervals were significantly longer in PTSD rats than in control and PTSDr rats. Only cardiomyocytes of PTSD rats had histomorphological signs of metabolic and hypoxic injury and impaired contractility. Oxidative stress markers were higher in PTSD than in PTSDr rats. Pro-inflammatory IL-6 was higher in PTSD rats than in control and PTSDr rats, and anti-inflammatory IL-4 was lower in PTSD than in control and PTSDr rats. Myocardial HSP70 was lower in PTSD rats than in PTSDr and control rats. Our conclusion was that rats with PTSD developed multiple signs of cardiac injury. PTSDr rats were resistant also to cardiac injury. Factors that limit cardiac damage in PS rats include reduced inflammation and oxidative stress and increased protective HSP70.NEW & NOTEWORTHY For the first time, rats exposed to stress were segregated into experimental PTSD (ePTSD)-susceptible and ePTSD-resistant rats. Cardiac injury, ECG changes, and impaired exercise tolerance were more pronounced in ePTSD-susceptible rats. Resistance to ePTSD was associated with decreased inflammation and oxidative stress and with increased protective heat shock protein 70. Results may help identify individuals at high risk of PTSD and also provide a foundation for developing preventive and therapeutic means to restrict PTSD-associated cardiac morbidity.

Offensive Behavior, Striatal Glutamate Metabolites, and Limbic-Hypothalamic-Pituitary-Adrenal Responses to Stress in Chronic Anxiety.

Variations in anxiety-related behavior are associated with individual allostatic set-points in chronically stressed rats. Actively offensive rats with the externalizing indicators of sniffling and climbing the stimulus and material tearing during 10 days of predator scent stress had reduced plasma corticosterone, increased striatal glutamate metabolites, and increased adrenal 11-dehydrocorticosterone content compared to passively defensive rats with the internalizing indicators of freezing and grooming, as well as to controls without any behavioral changes. These findings suggest that rats that display active offensive activity in response to stress develop anxiety associated with decreased allostatic set-points and increased resistance to stress.

Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder.

Hexobarbital sleep test (HST) was performed in male Wistar rats (hexobarbital 60 mg/kg, i.p.) 30 days prior to stress exposure. Based on the duration of hexobarbital-induced sleep, rats were divided into two groups, animals with high intensity (fast metabolizers (FM), sleep duration <15 min) or low intensity of hexobarbital metabolism (slow metabolizers (SM), sleep duration ≥15 min). The SM and FM groups were then divided into two subgroups: unstressed and stressed groups. The stressed subgroups were exposed to predator scent stress for 10 days followed by 15 days of rest. SM and FM rats from the unstressed group exhibited different behavioral and endocrinological patterns. SM showed greater anxiety and higher corticosterone levels. In stressed animals, anxiety-like posttraumatic stress disorder (PTSD) behavior was aggravated only in SM. Corticosterone levels in the stressed FM, PTSD-resistant rats, were lower than in unstressed SM. Thus, HST was able to predict the susceptibility or resistance to experimental PTSD, which was consistent with the changes in glucocorticoid metabolism.

High and low anxiety phenotypes in a rat model of complex post-traumatic stress disorder are associated with different alterations in regional brain monoamine neurotransmission.

BACKGROUND: Repeated exposure to predator scent stress (PSS) has been used as an animal model of complex post-traumatic stress disorder (CPTSD). The aim of the current study was to assess brain monoamines and their primary metabolites concentrations in male Wistar rats (16 control, 19 exposed to chronic PSS). METHODS: Rats were exposed to PSS for ten days. Fourteen days later, the rats' anxiety index (AI) was assessed with an elevated plus maze test; based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone levels were measured by radioimmunoassay. Brain monoamines and their metabolites were measured using high-performance liquid chromatography with electrochemical detector. RESULTS: PSS exposure led to a significant increase in average rats' AI and a reduction in plasma corticosterone levels. Medullar catecholamines and hippocampal and neocortical norepinephrine levels were increased, and pontine norepinephrine and cerebellar dopamine decreased in PSS-exposed rats. Cerebellar norepinephrine levels were increased, and midbrain, hippocampal, and neocortical 5-HT and hypothalamic and hippocampal dopamine levels-decreased in high-, but not in low-anxiety rats. The decrease in hippocampal dopamine levels was accompanied by an increase of DOPAC levels, suggesting and abnormal metabolism of this transmitter. CONCLUSION: Reductions in 5-HT and dopamine in mid- and forebrain brain areas are associated with stress susceptibility in rodents and perhaps also with PTSD vulnerability in humans. Dopamine and 5-HT metabolism and its modulation by glucocorticoids appear to play a role in stress susceptibility and in CPTSD.

Low glucocorticoids in stress-related disorders: the role of inflammation.

There is evidence that plasma cortisol concentration can be either increased or decreased in patients with depression and related anxiety and stress-related disorders; the exact pathophysiological mechanisms of this state are not almost clear. Several distinct theories were proposed and mechanisms, which could lead to decreased glucocorticoid signaling and/or levels, were described. However, there is a possible drawback in almost all the theories proposed: insufficient attention to the inflammatory process, which is undoubtedly present in several stress-related disorders, including post-traumatic stress disorder (PTSD). Previous studies only briefly mentioned the presence of an inflammatory reaction's signs in PTSD, without giving it due importance, although recognizing that it can affect the course of the disease. With that, the state of biochemical changes, characterized by the low glucocorticoids, glucocorticoid receptor's resistance and the signs of the persistent inflammation (with the high levels of circulating cytokines) might be observed not only in PTSD but in coronary heart diseases and systemic chronic inflammatory diseases (rheumatoid arthritis) as well. That is why the present review aims to depict the pathophysiological mechanisms, which lead to a decrease in glucocorticoids in PTSD due to the action of inflammatory stimuli. We described changes in the glucocorticoid system and inflammatory reaction as parts of an integral system, where glucocorticoids and the glucocorticoid receptor reside at the apex of a regulatory network that blocks several inflammatory pathways, while decreased glucocorticoid signaling and/or level leads to unchecked inflammatory reactions to promote pathologies such as PTSD. LAY SUMMARY This review emphasizes the importance of inflammatory reaction in the development of puzzling conditions sometimes observed in severe diseases including post-traumatic stress disorder - the decreased levels of glucocorticoids in the blood. Following the classical concepts, one would expect an increase in glucocorticoid hormones, since they are part of the feedback mechanism in the immune system, which reduces stress and inflammation. However, low levels of glucocorticoid hormones are also observed. Thus, this review describes potential mechanisms, which can lead to the development of such a state.

Intermittent Hypoxic Conditioning Alleviates Post-Traumatic Stress Disorder-Induced Damage and Dysfunction of Rat Visceral Organs and Brain.

Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC's ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day exposure to cat urine scent (PTSD rats). Some rats were then adapted to 14-day IHC (PTSD+IHC rats), while PTSD and untreated control rats were cage rested. PTSD rats had a higher anxiety index (AI, X-maze test), than control or PTSD+IHC rats. This higher AI was associated with reduced glycogen content and histological signs of metabolic and hypoxic damage and of impaired contractility. The livers of PTSD rats had reduced glycogen content. Liver and blood alanine and aspartate aminotransferase activities of PTSD rats were significantly increased. PTSD rats had increased norepinephrine concentration and decreased monoamine oxidase A activity in cerebral cortex. The PTSD-induced elevation of carbonylated proteins and lipid peroxidation products in these organs reflects oxidative stress, a known cause of organ pathology. IHC alleviated PTSD-induced metabolic and structural injury and reduced oxidative stress. Therefore, IHC is a promising preventive treatment for PTSD-related morphological and functional damage to organs, due, in part, to IHC's reduction of oxidative stress.

From Allostatic Load to Allostatic State-An Endogenous Sympathetic Strategy to Deal With Chronic Anxiety and Stress?

The concepts of allostatic load and overload, i. e., a dramatic increase in the allostatic load that predisposes to disease, have been extensively described in the literature. Here, we show that rats engaging in active offensive response (AOR) behavioral strategies to chronic predator scent stress (PSS) display less anxiety behavior and lower plasma cortisol levels vs. rats engaging in passive defensive response (PDR) behavioral strategies to chronic PSS. In the same chronic PSS paradigm, AOR rats also have higher lactate and lower glutamate levels in amygdala but not in control-region hippocampus vs. PDR rats. The implications of these findings for regulation of allostatic and stress responses, and post-traumatic stress disorder (PTSD) are discussed.

Chronic predator scent stress alters serotonin and dopamine levels in the rat thalamus and hypothalamus, respectively.

The aim of this study was to investigate the effect of chronic predator scent stress (PSS) on monoamine levels in rat thalamus and hypothalamus. Rats were exposed to the PSS (sand containing cat urine) for ten minutes daily for ten days. Control animals were exposed to the sand containing clean water. Fifteen days later, rats' behavior and thalamic and hypothalamic levels of monoamines were analyzed. PSS rats had elevated anxiety, increased thalamic serotonin and decreased hypothalamic dopamine concentrations. This decrease in hypothalamic dopamine may explain, at least in part, lowered corticosterone levels observed in PSS animals in our previous studies.

Correction to: Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms.

The original version of this article unfortunately contained a mistake in the co-author name.

Intermittent hypoxia improves behavioral and adrenal gland dysfunction induced by posttraumatic stress disorder in rats.

Nonpharmacological treatments of stress-induced disorders are promising, since they enhance endogenous stress defense systems, are free of side effects, and have few contraindications. The present study tested the hypothesis that intermittent hypoxia conditioning (IHC) ameliorates behavioral, biochemical, and morphological signs of experimental posttraumatic stress disorder (PTSD) induced in rats with a model of predator stress (10-day exposure to cat urine scent, 15 min daily followed by 14 days of stress-free rest). After the last day of stress exposure, rats were conditioned in an altitude chamber for 14 days at a 1,000-m simulated altitude for 30 min on day 1 with altitude and duration progressively increasing to 4,000 m for 4 h on day 5. PTSD was associated with decreased time spent in open arms and increased time spent in closed arms of the elevated X-maze, increased anxiety index, and increased rate of freezing responses. Functional and structural signs of adrenal cortex degeneration were also observed, including decreased plasma concentration of corticosterone, decreased weight of adrenal glands, reduced thickness of the fasciculate zone, and hydropic degeneration of adrenal gland cells. The thickness of the adrenal fasciculate zone negatively correlated with the anxiety index. IHC alleviated both behavioral signs of PTSD and morphological evidence of adrenal cortex dystrophy. Also, IHC alone exerted an antistress effect, which was evident from the increased time spent in open arms of the elevated X-maze and a lower number of rats displaying freezing responses. Therefore, IHC of rats with experimental PTSD reduced behavioral signs of the condition and damage to the adrenal glands. NEW & NOTEWORTHY Intermittent hypoxia conditioning (IHC) has been shown to be cardio-, vaso-, and neuroprotective. For the first time, in a model of posttraumatic stress disorder (PTSD), this study showed that IHC alleviated both PTSD-induced behavioral disorders and functional and morphological damage to the adrenal glands. Also, IHC alone exerted an antistress effect. These results suggest that IHC may be a promising complementary treatment for PTSD-associated disorders.

Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms.

Posttraumatic stress disorder (PTSD) is associated with myocardial injury, but changes in coronary regulatory mechanisms in PTSD have not been investigated. This study evaluated the effect of PTSD-inducing stress on coronary tone and its regulation by nitric oxide (NO) and voltage-gated K+ channels. PTSD was induced by exposing rats to predator stress, 15 min daily for 10 days, followed by 14 stress-free days. Presence of PTSD was confirmed by the elevated plus-maze test. Coronary tone was evaluated from changes in coronary perfusion pressure of Langendorff isolated hearts. Predator stress induced significant decreases in coronary tone of isolated hearts and in blood pressure of intact rats. L-NAME, a non-selective NO synthase (NOS) inhibitor, but not S-MT, a selective iNOS inhibitor, and increased coronary tone of control rats. In PTSD rats, both L-NAME and S-MT increased coronary tone. Therefore, the stress-induced coronary vasodilation resulted from NO overproduction by both iNOS and eNOS. NOS induction was apparently due to systemic inflammation as evidenced by increased serum interleukin-1ß and C-reactive protein in PTSD rats. Decreased corticosterone in PTSD rats may have contributed to inflammation and its effect on coronary tone. PTSD was also associated with voltage-gated K+ channel dysfunction, which would have also reduced coronary tone.

The role of microsomal oxidation in the regulation of monoamine oxidase activity in the brain and liver of rats.

It has been shown in our previous study that monoamine oxidase (MAO) activity in different brain regions are correlated with a microsomal oxidation phenotype. The data obtained in this study, using the microsomal oxidation inhibitor SKF525, and using animals with different duration of hexobarbital sleep, has shown that increased intensity of microsomal oxidation might be associated with increased MAO activity. Since the rats with short hexobarbital sleep time had higher content of hepatic microsomal cytochrome P450 than did rats with long hexobarbital sleep time. In addition, the rats with higher hepatic content of CYP450 had higher activities of MAO-A and MAO-B. Moreover, the microsomal oxidation inhibitor SKF-525 reduced brain and liver activities of MAOA and MAO-B. Consequently, MAO activities in a brain and a liver depend on the microsomal oxidation process.