2 research outputs found
Atrial natriuretic peptide in Cushing's disease.
No full textAtrial Natriuretic Peptide (ANF), is secreted by atrial myocytes in response to atrial stretch. Its plasma levels have been found elevated in conditions leading to salt and fluid repletion and consequent atrial distention. Recently, it has been demonstrated that dexamethasone can enhance ANF secretion, by acting on ANF gene expression and mRNA synthesis. High plasma levels of ANF have been observed in normal man after administration of cortisol and ACTH. In the case of glucocorticoid excess, as in Cushing's disease, limited and conflicting data are available. Therefore, we measured ANF basal values and ANF response to postural changes and volume expansion in eight patients with Cushing's disease. In our patients ANF values were higher than normals. ANF responded to volume expansion, 47.8 +/- 5.1 pg/ml before sodium load and 69.9 +/- 7.0 pg/ml after sodium load, and changed minimally after postural manoeuvres, 47.3 +/- 3.2 pg/ml supine and 41.7 +/- 5.1 pg/ml upright. These data indicate that ANF secretion is enhanced in Cushing's disease, and its regulation is partially altered. Since in this condition hypervolemia has not been certainly demonstrated, a direct relationship between elevated ANF and glucocorticoid excess could be suggested
Reprogramming astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site-deficient Ascl1
No full textCellular reprogramming of mammalian glia to an induced neuronal fate holds the potential for restoring diseased brain circuits. While the proneural factor achaete-scute complex-like 1 (Ascl1) is widely used for neuronal reprogramming, in the early postnatal mouse cortex, Ascl1 fails to induce the glia-to-neuron conversion, instead promoting the proliferation of oligodendrocyte progenitor cells (OPC). Since Ascl1 activity is posttranslationally regulated, here, we investigated the consequences of mutating six serine phospho-acceptor sites to alanine (Ascl1SA6) on lineage reprogramming in vivo. Ascl1SA6 exhibited increased neurogenic activity in the glia of the early postnatal mouse cortex, an effect enhanced by coexpression of B cell lymphoma 2 (Bcl2). Genetic fate-mapping revealed that most induced neurons originated from astrocytes, while only a few derived from OPCs. Many Ascl1SA6/Bcl2-induced neurons expressed parvalbumin and were capable of high-frequency action potential firing. Our study demonstrates the authentic conversion of astroglia into neurons featuring subclass hallmarks of cortical interneurons, advancing our scope of engineering neuronal fates in the brain.We are grateful to B. Rico (King’s college london) for support throughout the project. We acknowledge support from the Microscopy core Facility of the institute of Molecular Biology (iMB) Mainz. Funding: this research was funded in part by the Wellcome trust (206410/Z/17/Z). For the purpose of open access, the author has applied a cc BY public copyright license to any author- accepted manuscript version arising from this submission. this study was also supported by funding from the european Research council (eRc) under the european Union’s horizon 2020 Research and innovation Programme (grant agreement no. 101021560, iMAGine), the German Research Foundation (Be 4182/11- 1, project no. 357058359; cRc1080, project no. 221828878), an eRA- net neuron grant (Brain4Sight, 01eW2202), the research initiative of Rheinland- Pfalz at the Johannes Gutenberg University Mainz (ReAlity) to B.B.; by the inneruniversitäre Forschungsförderung Stufe i of the Johannes Gutenberg University Mainz to S.P.; and by core funding to the Francis crick institute from cancer Research United Kingdom, the Medical Research council, and the Wellcome trust (Fc001002). n.M. was supported by a fellowship from the human Frontiers Science Program (hFSP long- term Fellowship, lt000646/2015). F.F.S. was supported by a fellowship from São Paulo Research Foundation (FAPeSP) process no. 2021/13515- 5. c.S. holds the dixon Family chair in Ophthalmology Research. Author contributions: conceptualization: B.B. design of experiments: n.M., S.P., A.B.A., and B.B. Performed and analyzed in vivo experiments: n.M., S.P., A.B.A., c.G., F.F.S., and R.W. Performed and analyzed RnAscope experiments: S.P. and A.B.A. electrophysiology experiments: n.M. Formal analysis: n.M., S.P., and A.B.A. visualization: n.M., S.P., and B.B. Resources: c.S., M.K., and S.G. Supervision: B.B. Writing—original draft: n.M., S.P., A.B.A, and B.B. Writing—review and editing: All authors. Competing interests: Patent application for SB2021- 002 “Method and compositions for neuronal Reprogramming” has been submitted by the Sunnybrook Research institute and the Governing council of the University of toronto [US patent no. 18/568,747, filed 8 december 2023 (pending)]. c.S. is an author of the patent. the other authors declare they have no competing interests. Data and materials availability: the raw data supporting the conclusions of this article will be openly available from the King’s college london research data repository, KORdS, at doi: 10.18742/23911320. Any reagents that this study generated will be shared by the corresponding author upon reasonable request. All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials.Peer reviewe
