Showing papers on "Corticosterone published in 2022"

Male and Female C57BL/6 Mice Respond Differently to Awake Magnetic Resonance Imaging Habituation

Abstract: Traditionally, preclinical magnetic resonance imaging (MRI) has been performed in anesthetized animals. However, anesthesia has been shown to perturb normal brain function and physiology. Such effects limit our ability to detect subtle physiological alterations in disease models and treatment studies, thus hampering discovery and compromising generality of findings. Therefore, methods for awake animal MRI are needed to study the rodent brain in its natural physiological state, free of anesthetics. Current setups for awake animal MRI rely on restraining systems to avoid animal movement during scanning. To reduce restraint stress, animals are habituated to the scanner environment prior to MRI data collection. To date, however, most awake MRI studies employ male rodents only. This is a fundamental limitation as results obtained may be pertinent only to half of the population. We characterized training and habituation responses of male and female mice to provide improved, sex-dependent training procedures for awake mouse MRI. We recorded heart rate, monitored behavioral responses (body weight and fecal boli weight) and fecal corticosterone levels (FCM) as indicators of wellbeing and stress during a 14-day progressive habituation protocol. In addition, we also assessed discomfort levels and anxiety using the mouse grimace scale (MGS) and light/dark test (LDT), respectively. All scores were compared between both groups. We found that heart rate was significantly decreased after 10 and 11 days of training for both males and females, respectively. However, the specific time course for this decrease was significantly different between males and females, and females exhibited higher anxiety levels during habituation and 14 days after habituation than males. Lastly, we also found that mean FCM levels for both groups were decreased after 11 days of MRI habituation. The present work shows that mice can be successfully trained for extended MRI sessions which is necessary for many (particularly non-fMRI) studies. Importantly, we find that males and females differ in their response to awake MRI habituation, which should be considered in future awake MRI studies that aim to include male and female mice.

Effects of corticosterone on BDNF expression and mood behaviours in mice

Abstract: Stress hormones such as cortisol play a critical role in depressive disorders. Therefore, corticosterone has been used to develop a depression model in animals. Our previous studies found that the precursor of brain-derived neurotrophic factor (proBDNF) and its receptors are upregulated in depression in human and animal models. In the present study, we aimed to examine whether proBDNF and mature BDNF (mBDNF) are altered in the corticosterone-induced depression model in mice. Male and female mice were given corticosterone dissolved in 0.3% hydroxypropyl- β-cyclodextrin (β-CD) or vehicle (β-CD) in drinking water for 33 days. We have found that corticosterone induced depressive-like behaviours as reflected by increased immobility time in the tail suspension test and decreased grooming time in the splash test. Corticosterone also induced anxiety-like behaviours as represented by decreased entries into the central zone of the open field test and the open arms of the elevated plus maze test. We found that corticosterone administration resulted in differential changes of proBDNF and mature BDNF in different brain regions and peripheral tissues. ProBDNF was increased in the hippocampus and cerebellum, but no change was found in the prefrontal cortex and hypothalamus. Both proBDNF and mBDNF were significantly increased in the pituitary gland. In contrast, proBDNF was significantly decreased in the adrenal gland. There were no significant changes in proBDNF or mBDNF in other peripheral tissues, including the liver and sex organs. We conclude that the stress hormone corticosterone causes depressive behaviours but differentially regulates the processing of proBDNF in mice. ProBDNF may participate in the development of depression behaviours in corticosterone treated animals.

Individual variation in natural or manipulated corticosterone does not covary with circulating glucose in a wild bird.

Abstract: Animals respond to sudden challenges with a coordinated set of physiological and behavioral responses that enhance the ability to cope with stressors. While general characteristics of the vertebrate stress response are well described, it is not as clear how individual components covary between- or within-individuals. A rapid increase in glucocorticoids coordinates the stress response and one of the primary downstream results is an increase in glucose availability via reduced glucose utilization. Here, we asked whether between- and within-individual variation in corticosterone directly predicted variation in glucose. We collected 2,673 paired glucose and corticosterone measures from 776 tree swallows (Tachycineta bicolor) from four populations spanning the species range. In adults, glucose and corticosterone both increased during a standardized restraint protocol in all four populations. Moreover, in one population experimentally increasing a precursor that stimulates corticosterone release resulted in a further increase in both measures. In contrast, nestlings did not show a robust glucose response to handling or manipulation. Despite this group level variation, there was very little evidence in any population that between-individual variation in corticosterone predicted between-individual variation in glucose regulation. Glucose was moderately repeatable within-individuals, but within-individual variation in glucose and corticosterone were unrelated. Our results highlight the fact that a strong response in one aspect of the coordinated acute stress response (corticosterone) does not necessarily indicate that specific downstream components, such as glucose, will show similarly strong responses. These results have implications for understanding the evolution of integrated stress response systems.

Embryonic osteocalcin signaling determines lifelong adrenal steroidogenesis and homeostasis in the mouse

Abstract: Through their ability to regulate gene expression in most organs, glucocorticoid (GC) hormones influence numerous physiological processes and are therefore key regulators of organismal homeostasis. In bone, GC hormones inhibit expression of the hormone Osteocalcin for poorly understood reasons. Here, we show that in a classical endocrine feedback loop, osteocalcin in return enhanced the biosynthesis of GC as well as mineralocorticoid hormones (adrenal steroidogenesis) in rodents and primates. Conversely, inactivation of osteocalcin signaling in adrenal glands significantly impaired adrenal growth and steroidogenesis in mice. Embryo-made osteocalcin was necessary for normal Sf1 expression in fetal adrenal cells and adrenal cell steroidogenic differentiation and therefore determined the number of steroidogenic cells present in the adrenal glands of adult animals. Embryonic, not postnatal, osteocalcin also governed adrenal growth, adrenal steroidogenesis, blood pressure, electrolyte equilibrium, and the rise in circulating corticosterone levels during the acute stress response in adult offspring. This osteocalcin-dependent regulation of adrenal development and steroidogenesis occurred even in the absence of a functional hypothalamus/pituitary/adrenal axis and explains why osteocalcin administration during pregnancy promoted adrenal growth and steroidogenesis and improved the survival of adrenocorticotropic hormone signaling-deficient animals. This study reveals that a bone-derived embryonic hormone influences lifelong adrenal functions and organismal homeostasis in the mouse.

Acute stress and alcohol exposure during adolescence result in an anxious phenotype in adulthood: Role of altered glutamate/endocannabinoid transmission mechanisms.

Abstract: Background Stressful episodes and high alcohol consumption during adolescence are considered major risk factors for the development of psychiatric disorders in adulthood. Identification of mechanisms underlying these early events, which enhanced vulnerability to mental illness, is essential for both their prevention and treatment. Methods Male Wistar rats were used to investigate the long-term effects of early restraint stress and intermittent alcohol exposure (intragastric administration of 3 g/kg ethanol; 4 days/week for 4 weeks during adolescence) on anxiety-like behavior and the expression of signaling systems associated with emotional behaviors [e.g., corticosterone, fatty acid-derived molecules and endocannabinoid enzymes, glutamate receptor subunits, corticotropin releasing hormone receptors (CRHR1 and CRHR2) and neuropeptide Y receptors (NPY1R and NPYR2)] in the blood and amygdala. Results Overall, both stress and alcohol exposure during adolescence induced anxiogenic-like behaviors, increased plasma levels of corticosterone and increases in the amygdalar expression of the cannabinoid CB2 receptor and certain subunits of glutamate receptors (i.e., mGluR1, mGluR5 and NMDAR1) in young adult rats. In addition, there were specific main effects of alcohol exposure on the expression of the cannabinoid CB1 receptor, monoacylglycerol lipase (MAGL) and NPY2R in the amygdala, and significant increases were observed in rats exposed to alcohol. Interestingly, there were significant interaction effects between restraint stress and alcohol exposure on the expression of plasma 2-arachidonoyl glycerol (2-AG), and both CRHR1,2 and NPY1R in the amygdala. Thus, the restraint stress was associated with increased 2-AG levels, which was not observed in rats exposed to alcohol. The alcohol exposure was associated with an increased expression of CRHR1,2 but the restraint stress prevented these increases (stress alcohol rats). In contrast, NPY1R was only increased in rats exposed to stress and alcohol. Finally, we did not observe any potentiation of the behavioral and molecular effects by the combination of stress and alcohol, which is concordant with an overall ceiling effect on some of the variables. Conclusion Separate and combined early stress and alcohol induced a common anxious phenotype with increased corticosterone in adulthood. However, there were differences in the amygdalar expression of signaling systems involved in maladaptive changes in emotional behavior. Therefore, our results suggest the existence of partially different mechanisms for stress and alcohol exposures.

Effects of RU486 in Treatment of Traumatic Stress-Induced Glucocorticoid Dysregulation and Fear-Related Abnormalities: Early versus Late Intervention

Abstract: Central glucocorticoid receptor (GR) activity is enhanced following traumatic events, playing a key role in the stress-related cognitive abnormalities of posttraumatic stress disorder (PTSD). GR antagonists are expected to have potential as pharmacological agents to treat PTSD-related symptoms such as anxiety and fear memory disruption. However, an incubation period is usually required and stress-induced abnormalities do not develop immediately following the trauma; thus, the optimal intervention timing should be considered. Single prolonged stress (SPS) was employed as a rodent PTSD model to examine the effects of early or late (1–7 versus 8–14 days after the SPS) sub-chronic RU486 (a GR antagonist) administration. Behaviorally, fear conditioning and anxiety behavior were assessed using the fear-conditioning test and elevated T-maze (ETM), respectively. Neurochemically, the expressions of GR, FK506-binding proteins 4 and 5 (FKBP4 and FKBP5), and early growth response-1 (Egr-1) were assessed in the hippocampus, medial prefrontal cortex (mPFC), amygdala, and hypothalamus, together with the level of plasma corticosterone. Early RU486 administration could inhibit SPS-induced behavioral abnormalities and glucocorticoid system dysregulation by reversing the SPS-induced fear extinction deficit, and preventing SPS-reduced plasma corticosterone levels and SPS-induced Egr-1 overexpression in the hippocampus. Early RU486 administration following SPS also increased the FKBP5 level in the hippocampus and hypothalamus. Finally, both early and late RU486 administration inhibited the elevated hippocampal FKBP4 level and hypothalamus GR level in the SPS rats. Early intervention with a GR antagonist aids in the correction of traumatic stress-induced fear and anxiety dysregulation.

Acute stress and alcohol exposure during adolescence result in an anxious phenotype in adulthood: Role of altered glutamate/endocannabinoid transmission mechanisms

Abstract: Stressful episodes and high alcohol consumption during adolescence are considered major risk factors for the development of psychiatric disorders in adulthood. Identification of mechanisms underlying these early events, which enhanced vulnerability to mental illness, is essential for both their prevention and treatment.Male Wistar rats were used to investigate the long-term effects of early restraint stress and intermittent alcohol exposure (intragastric administration of 3 g/kg ethanol; 4 days/week for 4 weeks during adolescence) on anxiety-like behavior and the expression of signaling systems associated with emotional behaviors [e.g., corticosterone, fatty acid-derived molecules and endocannabinoid enzymes, glutamate receptor subunits, corticotropin releasing hormone receptors (CRHR1 and CRHR2) and neuropeptide Y receptors (NPY1R and NPYR2)] in the blood and amygdala.Overall, both stress and alcohol exposure during adolescence induced anxiogenic-like behaviors, increased plasma levels of corticosterone and increases in the amygdalar expression of the cannabinoid CB2 receptor and certain subunits of glutamate receptors (i.e., mGluR1, mGluR5 and NMDAR1) in young adult rats. In addition, there were specific main effects of alcohol exposure on the expression of the cannabinoid CB1 receptor, monoacylglycerol lipase (MAGL) and NPY2R in the amygdala, and significant increases were observed in rats exposed to alcohol. Interestingly, there were significant interaction effects between restraint stress and alcohol exposure on the expression of plasma 2-arachidonoyl glycerol (2-AG), and both CRHR1,2 and NPY1R in the amygdala. Thus, the restraint stress was associated with increased 2-AG levels, which was not observed in rats exposed to alcohol. The alcohol exposure was associated with an increased expression of CRHR1,2 but the restraint stress prevented these increases (stress alcohol rats). In contrast, NPY1R was only increased in rats exposed to stress and alcohol. Finally, we did not observe any potentiation of the behavioral and molecular effects by the combination of stress and alcohol, which is concordant with an overall ceiling effect on some of the variables.Separate and combined early stress and alcohol induced a common anxious phenotype with increased corticosterone in adulthood. However, there were differences in the amygdalar expression of signaling systems involved in maladaptive changes in emotional behavior. Therefore, our results suggest the existence of partially different mechanisms for stress and alcohol exposures.

Bacillus licheniformis Reshapes the Gut Microbiota to Alleviate the Subhealth

Abstract: Subhealth is a condition between health and disease that has become a common public health risk. Therefore, it is necessary to find more scientific therapies that can alleviate the symptoms of subhealth effectively. The gut microbiota is closely associated with subhealth. As a mature probiotic preparation, Bacillus licheniformis (B. licheniformis) can regulate gut microbiota balance, which indicates that B. licheniformis has the potential in regulating subhealth. This study produced the subhealthy rats by using chronic stress for 4 weeks to simulate psychological stress, with excessive antibiotics for 1 week to simulate bad living habits. Then, they were treated for 4 weeks with B. licheniformis. The results showed that B. licheniformis could recover the gut microbiota balance that had been destroyed by subhealth. The serum corticosterone and the proinflammatory cytokine tumor necrosis factor-α decreased after being treated by B. licheniformis. B. licheniformis also reduced glutamic acid and norepinephrine levels while increasing γ-aminobutyric acid and 5-hydroxytryptamine levels in the brain. In addition to the physiological changes, B. licheniformis decreased the anxiety-like behaviors of rats. Therefore B. licheniformis could alleviate the subhealth state, mainly by remodeling the gut microbiota, reducing inflammation, inhibiting the hypothalamic–pituitary–adrenal axis hyperactivity, regulating neurotransmitter levels, and easing a negative mood.

Acute stress induces an aberrant increase of presynaptic release of glutamate and cellular activation in the hippocampus of BDNFVal/Met mice

Abstract: Stressful life events are considered major risk factors for the development of several psychiatric disorders, though people differentially cope with stress. The reasons for this are still largely unknown but could be accounted for by individual genetic variants, previous life events, or the kind of stressors. The human brain‐derived neurotrophic factor (BDNF) Val66Met variant, which was found to impair intracellular trafficking and activity‐dependent secretion of BDNF, has been associated with increased susceptibility to develop several neuropsychiatric disorders, although there is still some controversial evidence. On the other hand, acute stress has been consistently demonstrated to promote the release of glutamate in cortico‐limbic regions and altered glutamatergic transmission has been reported in psychiatric disorders. However, it is not known if the BDNF Val66Met single‐nucleotide polymorphism (SNP) affects the stress‐induced presynaptic glutamate release. In this study, we exposed adult male BDNFVal/Val and BDNFVal/Met knock‐in mice to 30 min of acute restraint stress. Plasma corticosterone levels, glutamate release, protein, and gene expression in the hippocampus were analyzed immediately after the end of the stress session. Acute restraint stress similarly increased plasma corticosterone levels and nuclear glucocorticoid receptor levels and phosphorylation in both BDNFVal/Val and BDNFVal/Met mice. However, acute restraint stress induced higher increases in hippocampal presynaptic release of glutamate, phosphorylation of cAMP‐response element binding protein (CREB), and levels of the immediate early gene c‐fos of BDNFVal/Met compared to BFNFVal/Val mice. Moreover, acute restraint stress selectively increased phosphorylation levels of synapsin I at Ser9 and at Ser603 in BDNFVal/Val and BDNFVal/Met mice, respectively. In conclusion, we report here that the BDNF Val66Met SNP knock‐in mice display an altered response to acute restraint stress in terms of hippocampal glutamate release, CREB phosphorylation, and neuronal activation, compared to wild‐type animals. Taken together, these results could partially explain the enhanced vulnerability to stressful events of Met carriers reported in both preclinical and clinical studies.

Corticosterone induces discrete epigenetic signatures in the dorsal and ventral hippocampus that depend upon sex and genotype: focus on methylated Nr3c1 gene

Abstract: The genomic effects of circulating glucocorticoids are particularly relevant in cortico-limbic structures, which express a high concentration of steroid hormone receptors. To date, no studies have investigated genomic differences in hippocampal subregions, namely the dorsal (dHPC) and ventral (vHPC) hippocampus, in preclinical models treated with exogenous glucocorticoids. Chronic oral corticosterone (CORT) in mouse is a pharmacological approach that disrupts the activity of the hypothalamic-pituitary-adrenal axis, increases affective behavior, and induces genomic changes after stress in the HPC of wildtype (WT) mice and mice heterozygous for the gene coding for brain-derived neurotrophic factor Val66Met (hMet), a variant associated with genetic susceptibility to stress. Using RNA-sequencing, we investigated the genomic signatures of oral CORT in the dHPC and vHPC of WT and hMet male and female mice, and examined sex and genotype differences in response to oral CORT. Males under CORT showed lower glycemia and increased anxiety- and depression-like behavior compared to females that showed instead opposite affective behavior in response to CORT. Rank-rank-hypergeometric overlap (RRHO) was used to identify genes from a continuous gradient of significancy that were concordant across groups. RRHO showed that CORT-induced differentially expressed genes (DEGs) in WT mice and hMet mice converged in the dHPC of males and females, while in the vHPC, DEGs converged in males and diverged in females. The vHPC showed a higher number of DEGs compared to the dHPC and exhibited sex differences related to glucocorticoid receptor (GR)-binding genes and epigenetic modifiers. Methyl-DNA-immunoprecipitation in the vHPC revealed differential methylation of the exons 1C and 1F of the GR gene (Nr3c1) in hMet females. Together, we report behavioral and endocrinological sex differences in response to CORT, as well as epigenetic signatures that i) differ in the dHPC and vHPC,ii) are distinct in males and females, and iii) implicate differential methylation of Nr3c1 selectively in hMet females.

Chronic glucocorticoid exposure causes brown adipose tissue whitening, alters whole‐body glucose metabolism and increases tissue uncoupling protein‐1

Abstract: Adipose tissue (AT) has been found to exist in two predominant forms, white and brown. White adipose tissue (WAT) is the body's conventional storage organ, and brown adipose tissue (BAT) is responsible for non‐shivering thermogenesis which allows mammals to produce heat and regulate body temperature. Studies examining BAT and its role in whole‐body metabolism have found that active BAT utilizes glucose and circulating fatty acids and is associated with improved metabolic outcomes. While the beiging of WAT is a growing area of interest, the possibility of the BAT depot to “whiten” and store more triglycerides also has metabolic and health implications. Currently, there are limited studies that examine the effects of chronic stress and its ability to induce a white‐like phenotype in the BAT depot. This research examined how chronic exposure to the murine stress hormone, corticosterone, for 4 weeks can affect the whitening process of BAT in C57BL/6 male mice. Separate treatments with mirabegron, a known β3‐adrenergic receptor agonist, were used to directly compare the effects of corticosterone with a beiging phenotype. Corticosterone‐treated mice had significantly higher body weight (p ≤ 0.05) and BAT mass (p ≤ 0.05), increased adipocyte area (p ≤ 0.05), were insulin resistant (p ≤ 0.05), and significantly elevated expressions of uncoupling protein 1 (UCP‐1) in BAT (p ≤ 0.05) while mitochondrial content remained unchanged. This whitened phenotype has not been previously associated with increased uncoupling proteins under chronic stress and may represent a compensatory mechanism being initiated under these conditions. These findings have implications for the study of BAT in response to chronic glucocorticoid exposure potentially leading to BAT dysfunction and negative impacts on whole‐body glucose metabolism.

Transgenerational inheritance of fetal alcohol effects on proopiomelanocortin gene expression and methylation, cortisol response to stress, and anxiety-like behaviors in offspring for three generations in rats: Evidence for male germline transmission

Abstract: Previously it has been shown that fetal alcohol exposure increases the stress response partly due to lowering stress regulatory proopiomelanocortin (Pomc) gene expression in the hypothalamus via epigenetic mechanisms for multiple generations in mixed-breed rats. In this study we assess the induction of heritable epigenetic changes of Pomc-related variants by fetal alcohol exposure in isogenic Fischer 344 rats. Using transgenerational breeding models and fetal alcohol exposure procedures, we determined changes in hypothalamic Pomc gene expression and its methylation levels, plasma corticosterone hormone response to restraint stress, and anxiety-like behaviors using elevated plus maze tests in fetal alcohol-exposed offspring for multiple generations in isogenic Fischer rats. Fetal alcohol-exposed male and female rat offspring showed significant deficits in POMC neuronal functions with increased Pomc gene methylation and reduced expression. These changes in POMC neuronal functions were associated with increased plasma corticosterone response to restraint stress and increased anxiety-like behavior. These effects of fetal alcohol exposure persisted in the F1, F2, and F3 progeny of the male germline but not of the female germline. These data suggest that fetal alcohol exposure induces heritable changes in Pomc-related variants involving stress hyperresponsiveness and anxiety-like behaviors which perpetuate into subsequent generations through the male germline via epigenetic modifications.

Dim Blue Light at Night Induces Spatial Memory Impairment in Mice by Hippocampal Neuroinflammation and Oxidative Stress

Abstract: Light pollution is one of the most serious public problems, especially the night light. However, the effect of dim blue light at night (dLAN-BL) on cognitive function is unclear. In this study, we evaluated the effects of exposure to dLAN-BL in C57BL/6J mice for 4 consecutive weeks. Our results showed dLAN-BL significantly impaired spatial learning and memory and increased plasma corticosterone level in mice. Consistent with these changes, we observed dLAN-BL significantly increased the numbers and activation of microglia and the levels of oxidative stress product MDA in the hippocampus, decreased the levels of antioxidant enzymes Glutathione peroxidase (GSH-Px), Superoxide dismutase (SOD), Gluathione reductase (Gsr), total antioxidants (T-AOC) and the number of neurons in the hippocampus, up-regulated the mRNA expression levels of IL6, TNF-α and the protein expression levels of iNOS, COX2, TLR4, p-p65, Cleaved-Caspase3 and BAX, and down-regulated the mRNA expression levels of IL4, IL10, Psd95, Snap25, Sirt1, Dcx and the protein expression level of BCL2. In vitro results further showed corticosterone (10uM)-induced BV2 cell activation and up-regulated content of IL6, TNF-α in the cell supernatant and the protein expression levels of iNOS, COX2, p-p65 in BV2 cells. Our findings suggested dLAN-BL up-regulated plasma corticosterone level and hippocampal microglia activation, which in turn caused oxidative stress and neuroinflammation, leading to neuronal loss and synaptic dysfunction, ultimately leading to spatial learning and memory dysfunction in mice.

Sex Differences in Serotonin 5-HT 1A Receptor Responses to Repeated Restraint Stress in Adult Male and Female Rats

Abstract: Abstract Background Male and female rats were exposed to repeated restraint to determine how changes in serotonin (5-hydroxytryptamine; 5-HT) 1A receptors associate with stress hypothalamic-pituitary-adrenal (HPA) axis habituation. Methods In response to 2-hour episodes of restraint, repeated daily for 5 consecutive days, males and females displayed reliable declines in HPA output, indicated by diminished adrenocorticotropin and corticosterone secretory responses. Using the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) as a pharmacological challenge for inducing hypothermia and elevations in plasma corticosterone, males displayed sensitized hypothermal responses after repeated restraint, whereas corticosterone responses to 8-OH-DPAT were enhanced in both sexes following single or repeated exposure. Results Only males showed elevations in 5-HT 1A receptor G-protein coupling responses in the dorsal raphe after repeated restraint, whereas only females showed an increase in 5-HT 1A receptor responses in the hippocampus following single or repeated exposure. G-protein coupling responses within both regions correlated positively with 5-HT 1A receptor binding capacity. Thus, despite expressing similar capacities for stress HPA axis habituation, males and females emerged from repeated restraint to show region-specific changes in 5-HT 1A receptor function that may be explained, at least in part, by changes in receptor availability. Conclusions Based on the hypothermal and corticosteroid responses to 8-OH-DPAT, the present data suggest that stress habituation is met by an increase in the sensitivity of presynaptic 5-HT 1A receptors in males and by an increase in the sensitivity of a population of postsynaptic receptors in both sexes.

11β-Hydroxysteroid dehydrogenase 2: A key mediator of high susceptibility to osteoporosis in offspring after prenatal dexamethasone exposure

Abstract: Epidemiological investigations have shown that individuals treated with dexamethasone during pregnancy have an increased risk of osteoporosis after birth. Our studies reported that peak bone mass was decreased in the prenatal dexamethasone exposure (PDE) offspring before chronic stress, while further decrease was observed after chronic stress. Simultaneously, increase of bone local active corticosterone was observed in the PDE offspring, while further increase was also observed after chronic stress. Moreover, the histone H3 lysine 9 acetylation (H3K9ac) level of 11-beta hydroxysteroid dehydrogenase 2 (11β-HSD2) and its expression in bone tissue of PDE offspring rats remained lower than the control before and after birth. Injection of 11β-HSD2 overexpression lentivirus into the bone marrow cavity could partially alleviate the accumulation of bone local active corticosterone and bone loss induced by PDE. In vitro, dexamethasone inhibited the expression of 11β-HSD2 and aggravated the inhibitory effect of corticosterone on the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Overexpression of 11β-HSD2 partially alleviated the inhibitory effect of corticosterone. Moreover, dexamethasone promoted the nuclear translocation of glucocorticoid receptor (GR), which resulted in the stimulation of 11β-HSD2 expression due to the binding of GR to the 11β-HSD2 promoter region directly, as well as increasing H3K9ac level in the 11β-HSD2 promoter region by recruiting histone deacetylase 11 (HDAC11). Our results indicated that low expression of 11β-HSD2 in bone tissue is an important mediator for the high susceptibility to osteoporosis in PDE adult offspring.

Role of Sleep Restriction in Daily Rhythms of Expression of Hypothalamic Core Clock Genes in Mice

Abstract: Lack of sleep time is a menace to modern people, and it leads to chronic diseases and mental illnesses. Circadian processes control sleep, but little is known about how sleep affects the circadian system. Therefore, we performed a 28-day sleep restriction (SR) treatment in mice. Sleep restriction disrupted the clock genes’ circadian rhythm. The circadian rhythms of the Cry1 and Per1/2/3 genes disappeared. The acrophase of the clock genes (Bmal1, Clock, Rev-erbα, and Rorβ) that still had a circadian rhythm was advanced, while the acrophase of negative clock gene Cry2 was delayed. Clock genes’ upstream signals ERK and EIFs also had circadian rhythm disorders. Accompanied by changes in the central oscillator, the plasma output signal (melatonin, corticosterone, IL-6, and TNF-α) had an advanced acrophase. While the melatonin mesor was decreased, the corticosterone, IL-6, and TNF-α mesor was increased. Our results indicated that chronic sleep loss could disrupt the circadian rhythm of the central clock through ERK and EIFs and affect the output signal downstream of the core biological clock.

Curcumin ameliorated the mercuric chloride induced depression and anxiety in female mice offspring

Abstract: In the present investigation, the effect of mercuric chloride on gestation and lactation periods in mice was studied. The animals were treated with 10 ppm of HgCl2 and its complications were evaluated by supplementing 150 and 300 ppm of curcumin, respectively. Results indicated that HgCl2 increased depression-like behavior in treated animals compared to control and effects of depression in offspring significantly (p˂0.001) enhanced. Interestingly, the Tail suspension test clearly confirmed that the administration of curcumin enhanced the immobility (p˂0.001). The results confirmed that the curcumin administered mice spent less time in the closed arm (P < 0.001), whereas spent a very long time (P < 0.001) in the open arm. Related to the locomotor behaviors, number of squares crossed, wall rear, rear, and locomotion duration were decreased significantly (P < 0.001) while immobility duration was increased (P < 0.001) significantly compared to control. The anxiety and depression behaviors disorder due to mercuric chloride exposure indicated its availability via placenta or/and milk during lactation. The treatment with curcumin improved anxiety and depression behaviors compared to Hg experimental group.

The Antidepressant Effect of Deoiled Sunflower Seeds on Chronic Unpredictable Mild Stress in Mice Through Regulation of Microbiota–Gut–Brain Axis

Abstract: Objectives Sunflower seeds provide tryptophan-rich proteins with the potential to protect against depression. Tryptophan is a precursor of serotonin and a substrate for the production of indole derivatives by gut microbiota. This study aimed to investigate the association between the depression-alleviating effects of deoiled and dechlorogenic sunflower seeds (DSFS) and regulation of gut microbiota. Materials and Methods Male C57BL/6J mice were fed a diet comprising a source of soy protein (normal and model control), DSFS or whey protein concentrate (positive control) for 7 weeks, and chronic stress-induced depression was induced. Results Feeding the DSFS diet prevented depression-like behaviors, intestinal barrier damage, elevated plasma corticosterone, and reduced hippocampal serotonin levels in mice. Meanwhile, Feeding the DSFS diet significantly altered the gut microbiota structure, characterized by elevated relative abundances of Ileibacterium valens, Ruminococcus flavefaciens, Clostridium scindens, and Olsenella massiliensis, which were inversely associated with depressive behaviors and markers of mucosal barrier damage. DSFS also altered the gut metabolite profile, prevented depression-induced gut L-tryptophan depletion, and upregulated its metabolite indoleacetaldehyde. Conclusion Feeding the DSFS diet prevented depression in mice by remodeling the gut microbiota and bacterial tryptophan metabolism.