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While acute effects of GCs are adaptive, chronic GC exposure is increasingly recognized as an important factor contributing to the pathophysiology of neuropsychiatric disorders, such as post\u2010traumatic stress disorder (PTSD) or major depressive disorder (MDD). A piling evidence points to astrocytes as a central integrator of brain response to stress hormones, including GCs. In this review, we discuss a biphasic regulation of astrocyte metabolism by GCs. According to the hypothesis, astrocytes undergo metabolic adaptations in response to GC: acute exposure leads to the enhancement of astrocyte metabolism through upregulation of glycolysis, mitochondrial activation, and glutamate clearance. In turn, prolonged GC exposure induces a metabolic shift toward branched\u2010chain amino acid and lipid catabolism, promoting mitochondrial reactive oxygen species (ROS) production and impairing key homeostatic functions, including the astrocyte\u2010neuron lactate shuttle and calcium signaling. Progressive disruption of astrocytes' supporting function may subsequently lead to synaptic dysregulation and energy imbalance in stress\u2010related brain pathology. We postulate that a detailed understanding of this dynamic regulation is necessary for targeting astrocyte\u2010specific metabolic mechanisms in neuropsychiatric disorders.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70394-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70394","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:04:51Z","timestamp":1773032691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Astrocyte Bioenergetic Remodeling as a Central Trait of Disrupted Glucocorticoid Signaling: Mechanisms and Implications for Stress Vulnerability"],"prefix":"10.1111","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7337-3199","authenticated-orcid":false,"given":"Pawe\u0142","family":"Hanus","sequence":"first","affiliation":[{"name":"Department of Psychiatry Wroc\u0142aw Medical University  Wroclaw Poland"},{"name":"P4Health, \u0141ukasiewicz Research Network\u2013PORT Polish Center for Technology Development  Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Frydecka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Wroc\u0142aw Medical University  Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"\u015al\u0119zak","sequence":"additional","affiliation":[{"name":"P4Health, \u0141ukasiewicz Research Network\u2013PORT Polish Center for Technology Development  Wroclaw Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.4103\/1817\u20101737.65040"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.2003.02235.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnene.2011.00005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15811"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.007"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2024.1496163"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.05.034"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0026097"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4201"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21249"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1479"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481\u2010017\u20109752\u20107"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010025\u201001404\u20109"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.108"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2002690"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2013.00139"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00097.2012"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2024.106417"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22576"},{"key":"e_1_2_11_21_1","volume-title":"StatPearls","author":"Chaudhry H. 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