Chronic mild stress-induced dysregulation of MAPK and PI3K/AKT signaling in the hippocampus and medial prefrontal cortex of WKY female rats.

Wistar-Kyoto (WKY) rats subjected to chronic mild stress (CMS) represent a valid model of treatment-resistant depression (TRD). Considering that depression is more prevalent in women than in men, in the present study, female rats were used. We investigated the effect of CMS on behavior and different factors involved in neuroinflammatory processes and neuroplasticity in the hippocampus and medial prefrontal cortex (mPFC) of WKY female rats.

Sex-Related and Brain Regional Differences of URB597 Effects on Modulation of MAPK/PI3K Signaling in Chronically Stressed Rats.

Gender differences exist in depression incidence and antidepressant efficacy. In addition to the neurotransmission theory of depression, inflammation and disrupted signaling pathways play crucial roles in the pathophysiology of depression. Endocannabinoids offer a novel approach to treat inflammatory and emotional disorders like depression.

URB597 attenuates stress-induced ventricular structural remodeling by modulating cytokines, NF-κB, and JAK2/STAT3 pathways in female and male rats.

Endocannabinoids act as a stress response system; simultaneously, the modulation of this system has emerged a novel approach for the therapy of cardiovascular disorders. We investigated the protective effects of the chronic administration of the fatty acid amide hydrolase inhibitor URB597 on morphology, pro-inflammatory and anti-inflammatory cytokine, the cytoplasm-nuclear distribution of JAK2/STAT3, and NF-κB and Nrf2/HO-1 signaling in the left ventricle of female and male rats exposed to chronic unpredictable stress. Our results show that URB597 treatment exhibits an antidepressant-like effect, decreases the heart/body weight ratio, prevents the hypertrophy of cardiomyocytes, and reduces the increased level of IL-6 in the wall of the left ventricle of stressed female and male rats.

Sex specific effects of the fatty acid amide hydrolase inhibitor URB597 on memory and brain β-adrenergic and D1-dopamine receptors.

An increasing body of evidence shows significant sex differences in the mammalian brain in multiple behaviours and psychiatric and neurological diseases and as well as that the endocannabinoid system may differ between males and females. In this study we investigated sex differences in working, short-term and long-term memory and the expression of β-adrenergic and D1- and D2-receptors in the mPFC and hippocampus, brain regions that are involved in stress response and memory modulation in rats exposed to the chronic unpredictable stress (CUS) and the potential beneficial effects of the chronic fatty acid amide hydrolase inhibitor URB597 treatment. Chronically stressed male rats had an improvement of working memory, while stressed females showed very low object-recognition abilities.

Effects of Fatty Acid Amide Hydroxylase Inhibitor URB597 on the Catecholaminergic Activity of the Adrenal Medulla in Stressed Male and Female Rats.

Introduction: The present study examined the effects of fatty acid amide hydrolase inhibitor URB597 on the level of plasma catecholamine and their content, synthesis, and degradation in the adrenal medulla of male and female rats subjected to chronic unpredictable stress (CUS).

Material And Methods: Male and female Wistar rats were exposed to the 6 weeks of CUS and treated intraperitoneally with either 0.3 mg/kg/day of URB597 or vehicle in the last 2 weeks of stress protocol.

Inhibition of the fatty acid amide hydrolase changes behaviors and brain catecholamines in a sex-specific manner in rats exposed to chronic unpredictable stress.

Sex differences in the susceptibility to chronic unpredictable stress (CUS) and the effects of fatty acid amide hydrolase (FAAH) inhibitor URB597 in rats have been investigated in this study. In this context, we investigated the effects of prolonged treatment with URB597 on behavior, pro-inflammatory interleukin-6 (IL-6) and anti-inflammatory interleukin-10 (IL-10), catecholamine content and the expression of its biosynthetic and degrading enzymes in the hippocampus, hypothalamus and medial prefrontal cortex (mPFC) of rats subjected to CUS. The results show that CUS increases anxiety-like and depression-like behaviors but it was more pronounced in females.

The fatty acid amide hydrolase inhibitor URB597 modulates splenic catecholamines in chronically stressed female and male rats.

The changes in sympathetic innervations in lymphoid organs could be a key factor in immune dysregulation. The endocannabinoid system has been shown to exhibit potent immunomodulatory effects that may differ between males and females, representing a potential therapeutic target for peripheral and central inflammatory disorders. Thus, in the present study, an examination was made of the effect of fatty acid amide hydrolase inhibitor URB597 treatment on splenic catecholamine content, synthesis, uptake and degradation in chronically unpredictably stressed (CUS) female and male rats.

Melatonin treatment affects changes in adrenal gene expression of catecholamine biosynthesizing enzymes and norepinephrine transporter in the rat model of chronic-stress-induced depression.

This study investigated the effects of melatonin treatment on adrenal catecholamine content, synthesis, uptake, and vesicular transport induced by the chronic unpredictable mild stress (CUMS) model of depression in rats. This entailed quantifying the norepinephrine, epinephrine, mRNA, and protein levels of tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), phenylethanolamine -methyltransferase (PNMT), norepinephrine transporter (NET), and vesicular monoamine transporter 2 (VMAT2) in the adrenal medulla. CUMS caused a significant depletion of norepinephrine stores and protein levels of TH, DBH, and NET, whereas the gene expression of PNMT was increased.

Oxytocin modulates the expression of norepinephrine transporter, β-adrenoceptors and muscarinic M receptors in the hearts of socially isolated rats.

Social stress produces behavioral alterations, and autonomic and cardiac dysfunction in animals. In addition to the well-known roles of oxytocin on birth and maternal bonding, recent evidence shows that this neuropeptide possesses cardio-protective properties. However less is known about its role in the regulation of the autonomic nervous system.

Altered cardiac gene expression of noradrenaline enzymes, transporter and β-adrenoceptors in rat model of rheumatoid arthritis.

Baseline sympathetic activity was found to be elevated in rheumatoid arthritis (RA) patients and it is related to increased cardiovascular risk in these patients. Although many studies have highlighted the association between RA and increased cardiac sympathetic activity, the underlying mechanistic links remain unclear. The aim of the present study was to understand how diseases-triggered changes in gene expression may result in maladaptive physiological changes.

Melatonin mediated antidepressant-like effect in the hippocampus of chronic stress-induced depression rats: Regulating vesicular monoamine transporter 2 and monoamine oxidase A levels.

The hippocampus is sensitive to stress which activates norepinephrine terminals deriving from the locus coeruleus. Melatonin exerts positive effects on the hippocampal neurogenic process and on depressive-like behaviour. Thus, in the present study, an examination was made of the effect of chronic melatonin treatment on norepinephrine content, synthesis, uptake, vesicular transport and degradation in the hippocampus of rats exposed to CUMS.

Effects of oxytocin on adreno-medullary catecholamine synthesis, uptake and storage in rats exposed to chronic isolation stress.

Purpose/aim: The adreno-medullar system represents one of the main systems involved in the response to stressful events. The neuropeptide oxytocin, is highly sensitive to the social environment, and regulates autonomic function. Adreno-medullary activity is dependent on the synthesis of catecholamine, its reuptake, release, degradation and vesicular transport.

Differential regulation of catecholamine synthesis and transport in rat adrenal medulla by fluoxetine treatment.

We have recently shown that chronic fluoxetine treatment acted significantly increasing plasma norepinephrine and epinephrine concentrations both in control and chronically stressed adult male rats. However, possible effects of fluoxetine on catecholamine synthesis and re-uptake in adrenal medulla have been largely unknown. In the present study the effects of chronic fluoxetine treatment on tyrosine hydroxylase, a rate-limiting enzyme in catecholamine synthesis, as well as a norepinephrine transporter and vesicular monoamine transporter 2 gene expressions in adrenal medulla of animals exposed to chronic unpredictable mild stress (CUMS) for 4 weeks, were investigated.

Molecular basis of chronic stress-induced hippocampal lateral asymmetry in rats and impact on learning and memory.

Neurochemical lateralization has been demonstrated in the rat brain suggesting that such lateralization might contribute to behavior. Thus, the aim of the present study was to examine neurochemical asymmetry in the hippocampus, molecular basis of neurochemical lateralization and its impact on spatial learning and memory. Changes in noradrenaline content, tyrosine hydroxylase (TH) were studied in the right and left hippocampus of naive control and chronically isolated rats, by applying TaqMan RT-PCR and Western blot analysis.

Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats.

Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks.

Chronic fluoxetine treatment affects gene expression of catecholamine enzymes in the heart of depression model rats.

Depression is associated with increased risk of coronary heart diseases. Selective serotonin reuptake inhibitors (SSRIs) have been proved to be very effective in normalizing symptoms of depression, but the data on possible influence of these drugs on cardiovascular function is controversial. Applying Taqman RT-PCR assay, the effect of chronic treatment with a SSRI antidepressant fluoxetine has been investigated on gene expression of catecholamine biosynthetic enzymes in all four heart chambers of rats with signs of depression.

Hippocampal asymmetry in expression of catecholamine synthesizing enzyme and transporters in socially isolated rats.

Objectives: Right-left asymmetry of human brain function has been known for a century. Brain asymmetry and lateralization has been observed at the neurochemical level. At the neurochemical level, it is important to further correlate changes in monoaminergic activity with the synthesis and reuptake of these monoamines.

Forced exercise changes catecholamine synthesis in the spleen of adult rats.

Treadmill training produces modulation of neuro-endocrine and immune functions. This study examined the effects of chronic forced running (CFR) on the plasma concentration of catecholamines and the expression of splenic catecholamine biosynthetic enzymes in rats by using real-time RT-PCR and Western blot analyses. We found that CFR increases the plasma catecholamine levels, decreases splenic tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) mRNA levels and increases splenic PNMT protein levels.

Regulation of atrial catecholamine enzymes and adrenoceptor gene expression after chronic stress.

Chronic stress is a risk factor for the development of numerous psychopathological conditions in humans including depression. Changes in gene expression of tyrosine-hydroxylase (TH), dopamine-β-hydroxylase (DBH) phenylethanolamine N-methyltransferase (PNMT), β1-, β2- and β3-adrenoceptors in right and left rat atria upon chronic unpredictable mild stress (CMS) were investigated. CMS decreased TH and DBH gene expression levels both in right and left atria and increased PNMT mRNA in left atria.

Modulation of catecholamine-synthesizing enzymes in adrenal medulla and stellate ganglia by treadmill exercise of stressed rats.

The sympatho-adrenal system represents one of the main systems involved in the response to stressful events because its stress-induced activation results in an increased release of catecholamines. Exercise training acts as an important modulator of sympatho-adrenal system, adrenal medulla and stellate ganglia being two components of this system. This study aimed at investigating physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase in the adrenal medulla and stellate ganglia of chronically psychosocially stressed adult rats exposed daily to 20-min treadmill exercise for 12 weeks, using TaqMan RT-PCR assay.

Do RCAN1 proteins link chronic stress with neurodegeneration?

It has long been suspected that chronic stress can exacerbate, or even cause, disease. We now propose that the RCAN1 gene, which can generate several RCAN1 protein isoforms, may be at least partially responsible for this phenomenon. We review data showing that RCAN1 proteins can be induced by multiple stresses, and present new data also implicating psychosocial/emotional stress in RCAN1 induction.

Subsequent stress increases gene expression of catecholamine synthetic enzymes in cardiac ventricles of chronic-stressed rats.

Since previous experience of stressful situation profoundly affects response to a subsequent novel stressor, we examined changes in gene expression and protein levels of catecholamine biosynthetic enzymes in cardiac ventricles after exposure of chronic psychosocially isolated adult Wistar male rats to short-term immobilization stress. Chronic social isolation did not affect gene expression of tyrosine hydroxylase (TH) in either right or left ventricle. Subsequent immobilization of these animals produced an elevation of TH mRNA level in right and left ventricles.

Chronic individual housing-induced stress decreased expression of catecholamine biosynthetic enzyme genes and proteins in spleen of adult rats.

Objective: Social isolation is regarded as one of the most relevant causes of diseases in mammalian species. The activation of the sympathoneural system represents one of the key components of the stress response. The sympathetic nervous system is one of the major pathways involved in immune-neuroendocrine interactions.

Psychosocial stress-related changes in gene expression of norepinephrine biosynthetic enzymes in stellate ganglia of adult rats.

In this study we investigated the changes in norepinephrine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) gene expression in the stellate ganglia of naive controls and long-term socially isolated (12 weeks) adult rats and the response of these animals to additional immobilization stress. Psychosocial stress produced a significant increase of both TH mRNA and DBH mRNA levels in stellate ganglia. Additional immobilization of long-term psychosocially stressed rats expressed no effect on gene expression of these enzymes.

Chronic isolation of adult rats decreases gene expression of catecholamine biosynthetic enzymes in adrenal medulla.

Objective: Isolation of adult animals represents a form of psychsocial stress that produces sympatho-adrenomedullar activation. The aim of this work was to investigate the changes in gene expression and protein levels of catecholamine biosynthetic enzymes: tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in the adrenal medulla of naive control and chronically (12 weeks) socially isolated adult Wistar rat males and the response of these animals to additional immobilization stress (2 h).

Methods: TH, DBH and PNMT mRNA levels were quantified by quantitative real-time RT-PCR (qRT-PCR).