Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish
Exposure to excess glucocorticoid (GC) during early development is implicated in adult dysfunctions. Reduced adult hippocampal neurogenesis is a well-known consequence of exposure to early life stress or elevated GC, however the effects on neurogenesis during development and effects on other brain r...
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sg-ntu-dr.10356-1795962024-08-12T15:32:02Z Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish Eachus, Helen Choi, Min-Kyeung Tochwin, Anna Kaspareit, Johanna Ho, May Ryu, Soojin School of Biological Sciences Medicine, Health and Life Sciences Hypothalamus Nervous system development Exposure to excess glucocorticoid (GC) during early development is implicated in adult dysfunctions. Reduced adult hippocampal neurogenesis is a well-known consequence of exposure to early life stress or elevated GC, however the effects on neurogenesis during development and effects on other brain regions are not well understood. Using an optogenetic zebrafish model, here we analyse the effects of GC exposure on neurogenesis during development in the whole brain. We identify that the hypothalamus is a highly GC-sensitive region where elevated GC causes precocious development. This is followed by failed maturation and early decline accompanied by impaired feeding, growth, and survival. In GC-exposed animals, the developmental trajectory of hypothalamic progenitor cells is strikingly altered, potentially mediated by direct regulation of transcription factors such as rx3 by GC. Our data provide cellular and molecular level insight into GC-induced alteration of the hypothalamic developmental trajectory, a process crucial for health across the life-course. Nanyang Technological University Published version This project is supported by an award from The Dennis and Mireille Gillings Foundation to S.R. and the German Federal Office for Education Research (grant number 01GQ1404) to S.R. H.E. received support from the Society for Endocrinology and Wellcome Trust Institutional Strategic Support Fund 3 scheme (ISSF3) to Translational Research Exchange @ Exeter. M.H. received support from the CN Yang Scholars Programme at Nanyang Technological University. 2024-08-12T07:55:06Z 2024-08-12T07:55:06Z 2024 Journal Article Eachus, H., Choi, M., Tochwin, A., Kaspareit, J., Ho, M. & Ryu, S. (2024). Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish. Communications Biology, 7(1), 416-. https://dx.doi.org/10.1038/s42003-024-06060-5 2399-3642 https://hdl.handle.net/10356/179596 10.1038/s42003-024-06060-5 38580727 2-s2.0-85189880032 1 7 416 en Communications Biology © 2024 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. application/pdf |
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Medicine, Health and Life Sciences Hypothalamus Nervous system development Eachus, Helen Choi, Min-Kyeung Tochwin, Anna Kaspareit, Johanna Ho, May Ryu, Soojin Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish |
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Exposure to excess glucocorticoid (GC) during early development is implicated in adult dysfunctions. Reduced adult hippocampal neurogenesis is a well-known consequence of exposure to early life stress or elevated GC, however the effects on neurogenesis during development and effects on other brain regions are not well understood. Using an optogenetic zebrafish model, here we analyse the effects of GC exposure on neurogenesis during development in the whole brain. We identify that the hypothalamus is a highly GC-sensitive region where elevated GC causes precocious development. This is followed by failed maturation and early decline accompanied by impaired feeding, growth, and survival. In GC-exposed animals, the developmental trajectory of hypothalamic progenitor cells is strikingly altered, potentially mediated by direct regulation of transcription factors such as rx3 by GC. Our data provide cellular and molecular level insight into GC-induced alteration of the hypothalamic developmental trajectory, a process crucial for health across the life-course. |
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School of Biological Sciences |
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School of Biological Sciences Eachus, Helen Choi, Min-Kyeung Tochwin, Anna Kaspareit, Johanna Ho, May Ryu, Soojin |
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Article |
author |
Eachus, Helen Choi, Min-Kyeung Tochwin, Anna Kaspareit, Johanna Ho, May Ryu, Soojin |
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Eachus, Helen |
title |
Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish |
title_short |
Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish |
title_full |
Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish |
title_fullStr |
Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish |
title_full_unstemmed |
Elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish |
title_sort |
elevated glucocorticoid alters the developmental dynamics of hypothalamic neurogenesis in zebrafish |
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2024 |
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https://hdl.handle.net/10356/179596 |
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1814047233276903424 |