{"id":456331,"date":"2025-09-27T21:46:22","date_gmt":"2025-09-27T21:46:22","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/456331\/"},"modified":"2025-09-27T21:46:22","modified_gmt":"2025-09-27T21:46:22","slug":"infant-brain-gene-regulator-may-predispose-adults-to-dementia","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/456331\/","title":{"rendered":"Infant Brain Gene Regulator May Predispose Adults to Dementia"},"content":{"rendered":"<p><strong>Summary: <\/strong>A new study reveals that the brain\u2019s vulnerability to disorders like multiple sclerosis and dementia may begin in early life. Researchers identified a developmental \u201cswitch\u201d in astrocytes, the brain\u2019s support cells, governed by the NR3C1 gene.<\/p>\n<p>This switch epigenetically programs astrocytes to restrain inflammation in adulthood; without it, immune genes stay primed, making the brain overreact to inflammatory triggers. The findings highlight a critical early window that shapes lifelong brain health and suggest new therapeutic targets for neuroinflammatory and degenerative diseases.<\/p>\n<p><strong>Key Facts<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li><strong>Astrocyte Switch:<\/strong> The NR3C1 gene regulates early immune restraint in brain support cells.<\/li>\n<li><strong>Epigenetic Memory:<\/strong> Loss of NR3C1 leaves immune genes \u201copen,\u201d driving excessive inflammation later.<\/li>\n<li><strong>Disease Link:<\/strong> Findings connect early astrocyte programming to risks for MS, Alzheimer\u2019s, and dementia.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>KAIST<\/p>\n<p><strong>Why do some people remain healthy through childhood yet become more vulnerable to brain disorders such as dementia later in life? <\/strong><\/p>\n<p>A KAIST (President Kwang Hyung Lee) -led team has uncovered a key part of the answer: a developmental \u2018switch\u2019 in astrocytes\u2014the brain\u2019s most abundant support cells that shapes how strongly the brain\u2019s immune system reacts in adulthood.<\/p>\n<p>  <img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"799\" src=\"https:\/\/www.europesays.com\/uk\/wp-content\/uploads\/2025\/09\/astrocyte-inflammation-neurodevelopment.jpg\" alt=\"This shows astrocytes.\"  \/> In effect, NR3C1 serves as an early \u2018brake\u2019 that prevents over-activation of astrocyte immune programs in adulthood. Credit: Neuroscience News<\/p>\n<p>The study identifies a gene,\u00a0NR3C1\u00a0(encoding the glucocorticoid receptor), as a master regulator of this switch and shows how early-life epigenetic \u2018memory\u2019 can predispose the adult brain to excessive inflammation.<\/p>\n<p>The work was carried out by a joint team led by Professor Inkyung Jung (Department of Biological Sciences, KAIST) and Associate Director Won-Suk Chung (Center for Vascular Research, Institute for Basic Science; Professor, KAIST Biological Sciences).<\/p>\n<p>Using mouse models, the researchers mapped gene-regulatory programs across multiple stages of astrocyte development and found that\u00a0NR3C1\u00a0acts during a brief early-postnatal window to enforce long-term immune restraint.<\/p>\n<p>To build this map, the team combined state-of-the-art 3D epigenome profiling with RNA sequencing and chromatin accessibility analyses, capturing how DNA folds and which regulatory elements contact target genes. They identified 55 stage-specific transcription factors that guide astrocyte maturation; among them, NR3C1 emerged as the critical \u2018switch\u2019 in early life.<\/p>\n<p>Notably, deleting NR3C1 in astrocytes did not disrupt normal development. However, when the adult mice were challenged with an autoimmune model of multiple sclerosis, animals lacking astrocytic NR3C1 mounted exaggerated inflammatory responses and developed more severe disease.<\/p>\n<p>Mechanistically, the study shows that early loss of\u00a0NR3C1\u00a0epigenetically primes immune genes \u2013 keeping their regulatory elements open and ready \u2013 so that later in life these genes respond too strongly to inflammatory cues. In effect, NR3C1 serves as an early \u2018brake\u2019 that prevents over-activation of astrocyte immune programs in adulthood.<\/p>\n<p>\u201cThis is the first demonstration that astrocyte immune functions are governed by epigenetic memory,\u201d said Professor Won-Suk Chung. \u201cOur findings offer new clues to the origins of degenerative brain disorders, including Alzheimer\u2019s disease.\u201d<\/p>\n<p>\u201cWe reveal a temporal regulatory window in astrocyte development that can set the stage for disease vulnerability in adulthood,\u201d added Professor Inkyung Jung.<\/p>\n<p>\u201cUnderstanding the 3D genome logic behind these programs could open paths to therapies for immune-related brain disorders such as multiple sclerosis.\u201d<\/p>\n<p>The results of this study were published online on September 22 in the international journal\u00a0Nature Communications\u00a0(IF 15.7), with Dr. Seongwan Park and PhD student Hyeonji Park of KAIST\u2019s Department of Biological Sciences as co-first authors.<\/p>\n<p><strong>Funding: <\/strong>This research was supported by the Suh Kyungbae Science Foundation, the Ministry of Health and Welfare, the Ministry of Science and ICT, and IBS.<\/p>\n<p>About this genetics, neurology, and neurodevelopment research news<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#d0bab5b5b8a9a5bebcb5b590bbb1b9a3a4feb1b3febba2\" target=\"_blank\" rel=\"noreferrer noopener\">JEEHYUN LEE<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/kaist.ac.kr\" target=\"_blank\" rel=\"noreferrer noopener\">KAIST<\/a><br \/><strong>Contact: <\/strong>JEEHYUN LEE \u2013 KAIST<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/www.nature.com\/articles\/s41467-025-64088-5\" target=\"_blank\" rel=\"noreferrer noopener\">NR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice<\/a>\u201d by Inkyung Jung et al. Nature Communications<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>NR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice<\/strong><\/p>\n<p>Astrocytes are critical contributors to brain disorders, yet the mechanisms underlying their selective vulnerability to specific diseases remain poorly understood.<\/p>\n<p>Here, we demonstrate that NR3C1 acts as a key regulator of early postnatal astrocyte development, shaping long-term immune responses in mice.<\/p>\n<p>Through integrative analyses of gene expression, chromatin accessibility, and long-range chromatin interactions, we identify 55 stage-specific TFs, with NR3C1 uniquely associated with early postnatal maturation.<\/p>\n<p>Although mice lacking astrocytic NR3C1 exhibit no detectable developmental abnormalities, these mice display heightened susceptibility to exacerbated immune responses following adult-onset experimental autoimmune encephalomyelitis (EAE).<\/p>\n<p>Many of the dysregulated EAE response genes are linked to candidate\u00a0cis-regulatory elements altered by early NR3C1 loss, driving exacerbated inflammatory responses.<\/p>\n<p>Notably, only NR3C1 depletion during early, but not late, astrocyte development induces long-lasting epigenetic reprogramming that primes astrocytic immune responses.<\/p>\n","protected":false},"excerpt":{"rendered":"Summary: A new study reveals that the brain\u2019s vulnerability to disorders like multiple sclerosis and dementia may begin&hellip;\n","protected":false},"author":2,"featured_media":456332,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3846],"tags":[113645,1153,648,215,425,649,267,39280,219,654,233,220,153078,70,16,15],"class_list":{"0":"post-456331","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-astrocytes","9":"tag-brain-aging","10":"tag-brain-development","11":"tag-brain-research","12":"tag-dementia","13":"tag-developmental-neuroscience","14":"tag-genetics","15":"tag-kaist","16":"tag-neurobiology","17":"tag-neurodevelopment","18":"tag-neurology","19":"tag-neuroscience","20":"tag-nr3c1","21":"tag-science","22":"tag-uk","23":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/115278459280387921","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/456331","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=456331"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/456331\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/456332"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=456331"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=456331"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=456331"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}