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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Main Authors: Eachus, Helen, Choi, Min-Kyeung, Tochwin, Anna, Kaspareit, Johanna, Ho, May, Ryu, Soojin
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/179596
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Institution: Nanyang Technological University
Language: English
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spelling 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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
Hypothalamus
Nervous system development
spellingShingle 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
description 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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Eachus, Helen
Choi, Min-Kyeung
Tochwin, Anna
Kaspareit, Johanna
Ho, May
Ryu, Soojin
format Article
author Eachus, Helen
Choi, Min-Kyeung
Tochwin, Anna
Kaspareit, Johanna
Ho, May
Ryu, Soojin
author_sort 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
publishDate 2024
url https://hdl.handle.net/10356/179596
_version_ 1814047233276903424