Gravitational Collapse and Disk Formation in Magnetized Cores

We discuss the effects of the magnetic field observed in molecular clouds on the process of star formation, concentrating on the phase of gravitational collapse of low-mass dense cores, cradles of sunlike stars. We summarize recent analytic work and numerical simulations showing that a substantial level of magnetic field diffusion at high densities has to occur in order to form rotationally supported disks. Furthermore, newly formed accretion disks are threaded by the magnetic field dragged from the parent core during the gravitational collapse. These disks are expected to rotate with a sub-Keplerian speed because they are partially supported by magnetic tension against the gravity of the central star. We discuss how sub-Keplerian rotation makes it difficult to eject disk winds and accelerates the process of planet migration. Moreover, magnetic fields modify the Toomre criterion for gravitational instability via two opposing effects: magnetic tension and pressure increase the disk local stability, but sub-Keplerian rotation makes the disk more unstable. In general, magnetized disks are more stable than their nonmagnetic counterparts; thus, they can be more massive and less prone to the formation of giant planets by gravitational instability.Comment: Chapter 16 in "Magnetic Fields in Diffuse Media", Springer-Verlag, eds. de Gouveia Dal Pino, E., Lazarian, A., Melioli,

Role of adrenal renin in the regulation of adrenal steroidogenesis corticotropin

The major regulator of mineralocorticoid production in the adrenal is angiotensin II produced by the action of renal renin. The discovery that the rodent adrenal also synthesizes renin and angiotensinogen suggests there is autocrine regulation of mineralocorticoid synthesis. The transgenic rat [TGR(mREN2)27] expresses the Ren-2d gene predominantly in the adrenal. Despite suppressed kidney and plasma renin, these animals develop fulminant hypertension between 5 and 15 weeks of age. Corticosteroid concentrations are significantly elevated during hypertension development. We assessed steroidogenesis in TGR(mREN2)27 rats by analyzing the expression of the mRNAs for three steroidogenic enzymes: P450scc, the rate-limiting step of steroidogenesis; P450c11 beta, which converts deoxycorticosterone to corticosterone in the zona fasciculata/reticularis; and P450c11AS, which converts deoxycorticosterone to aldosterone in the zona glomerulosa. P450c11AS mRNA, but neither P450c11 beta nor P450scc mRNA, was overexpressed in the adrenal gland of TGR(mREN2)27 rats. In situ hybridization with specific probes for P450c11 beta and P450c11AS mRNA localized the former exclusively to the zona fasciculata and the latter to the zona glomerulosa. In TGR(mREN2)27 rats, the size of the adrenal and number of P450c11AS-expressing zona glomerulosa cells were about twice those of a normal Sprague-Dawley rat. Both animals respond to corticotropin similarly; corticotropin had no effect on the expression of P450scc and P45011 beta mRNAs, rendered P450c11AS mRNA undetectable, and simultaneously altered the morphology of the adrenal cortex, resulting in a lack of zona glomerulosa-like cells. Thus, the local renin-angiotensin system has a major effect on the basal expression of P450c11AS mRNA, but little effect on the corticotropin-regulated expression of P450scc, P450c11 beta, and P450c11AS mRNAs

Targeted ablation of pituitary pre-proopiomelanocortin cells by herpes simplex virus-1 thymidine kinase differentially regulates mRNAs encoding the adrenocorticotropin receptor and aldosterone synthase in the mouse adrenal gland

We have produced and characterized lines of transgenic mice expressing a fusion gene composed of the pituitary expression-specific promoter region of the POMC gene, driving the herpes simplex viral-1 thymidine kinase. Adult mice were treated with the antiherpes agent ganciclovir at 70 mg/kg body weight (ip, twice daily for 10-12 days). Approximately 98% of the pituitary intermediate lobe melanotropes and anterior lobe corticotropes were ablated as determined by immunocytochemistry and RIA specific for the POMC-derived peptides, ACTH, beta-endorphin, and alpha-MSH. The number of lactotropes, somatotropes, thyrotropes, and gonadotropes was not altered compared with controls, indicating that in the adult pituitary, POMC products are not required to maintain the distribution of cell types. As expected, plasma corticosterone levels were substantially decreased after POMC cell ablation. In situ hybridization studies showed that the mouse ACTH receptor was expressed uniformly throughout the adrenal cortex, and RNase protection assays revealed that the ACTH receptor mRNA decreased after pituitary POMC cell ablation. Additionally, RNase protection assays showed that pituitary POMC cell ablation resulted in the decrease of adrenal p450c11 beta transcripts while p450c11AS (aldosterone synthase) mRNA levels remained constant. These data demonstrate differential regulation of steroid pathway-specific enzymes by POMC products. Our results also suggest that the thymidine kinase cell obliteration technique may not be dependent on cell division as a prerequisite for cytotoxicity, thus supporting the idea that targeted molecular ablation using cell- and tissue-specific promoter sequences to drive viral thymidine kinase expression can be refined further to study other nonmitotic cells

Regulation of structural plasticity and neurogenesis during stress and diabetes; protective effects of glucocorticoid receptor antagonists

In this chapter, we will review changes in structural plasticity of the adult hippocampus during stress and exposure to glucocorticoids (GCs). We further discuss the protective and normalizing role of glucocorticoid receptor (GR) antagonist treatment under these conditions and its implications for disorders such as depression and diabetes mellitus

Dysregulated relationship of inflammation and oxidative stress in major depression

► The relationship of inflammation to oxidation may be disturbed in untreated major depression; this may reflect or contribute to increased risk of co-morbid medical illnesses. Chronic inflammation and oxidative stress have been implicated in the pathophysiology of Major Depressive Disorder (MDD), as well as in a number of chronic medical conditions. The aim of this study was to examine the relationship between peripheral inflammatory and oxidative stress markers in un-medicated subjects with MDD compared to non-depressed healthy controls and compared to subjects with MDD after antidepressant treatment. We examined the relationships between IL-6, IL-10, and the IL-6/IL-10 inflammatory ratio vs. F2-isoprostanes (F2-IsoP), a marker of oxidative stress, in un-medicated MDD patients (n=20) before and after 8weeks of open-label sertraline treatment (n=17), compared to healthy non-depressed controls (n=20). Among the un-medicated MDD subjects, F2-IsoP concentrations were positively correlated with IL-6 concentrations (p<0.05) and were negatively correlated with IL-10 concentrations (p<0.01). Accordingly, F2-IsoP concentrations were positively correlated with the ratio of IL-6/IL-10 (p<0.01). In contrast, in the control group, there were no significant correlations between F2-IsoPs and either cytokine or their ratio. After MDD subjects were treated with sertraline for 8weeks, F2-IsoPs were no longer significantly correlated with IL-6, IL-10 or the IL-6/IL-10 ratio. These data suggest oxidative stress and inflammatory processes are positively associated in untreated MDD. Our findings are consistent with the hypothesis that the homeostatic buffering mechanisms regulating oxidation and inflammation in healthy individuals become dysregulated in untreated MDD, and may be improved with antidepressant treatment. These findings may help explain the increased risk of comorbid medical illnesses in MDD

Metabolomic analysis of male combat veterans with post traumatic stress disorder

10.1371/journal.pone.0213839PLoS ONE143e021383