Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors
Stress exposure is associated with the development of anxiety disorders, and astrocytes have emerged as critical mediators of stress responses and anxiety pathogenesis. While astrocytic dysfunction has been implicated in these processes, the specific molecular mechanisms remain elusive. In this stud...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-10-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025003302 |
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| author | Cheng-Lin Lu Jing Ren Wei Wang Liang-Yu Chen Xiao-Ying Lian Xiong Cao |
| author_facet | Cheng-Lin Lu Jing Ren Wei Wang Liang-Yu Chen Xiao-Ying Lian Xiong Cao |
| author_sort | Cheng-Lin Lu |
| collection | DOAJ |
| description | Stress exposure is associated with the development of anxiety disorders, and astrocytes have emerged as critical mediators of stress responses and anxiety pathogenesis. While astrocytic dysfunction has been implicated in these processes, the specific molecular mechanisms remain elusive. In this study, we demonstrate a crucial role for astrocytic glucocorticoid receptors (GRs) in the ventral hippocampus (vHPC) in modulating anxiety-like behaviors. We found that chronic restraint stress specifically reduced the GR expression in the vHPC, with no significant changes observed in the amygdala or dorsal hippocampus. Consistent with this finding, chronic corticosterone administration was found to induce anxiety-like behaviors in mice, accompanied by a significant reduction in the GR expression in the vHPC. The GR reduction, while prominent and functionally significant in astrocytes, is not exclusive to them in the vHPC under these stress conditions. Targeted deletion of GRs in astrocytes resulted in the development of anxiety-like behaviors in mice. Notably, selective ablation of astrocytic GRs specifically within the vHPC region produced similar behavioral phenotypes. RNA sequencing analysis of the vHPC from astrocytic GR-depletion mice identified potential molecular mechanisms underlying the pathomechanisms of astrocytic GRs in anxiety. These findings establish a novel pathway through which astrocytic GRs in the vHPC regulate anxiety-like behaviors, providing new insights into the neurobiological basis of stress-related anxiety disorders and identifying potential therapeutic targets. |
| format | Article |
| id | doaj-art-85fee5bc70a14e61ae89f349174459ab |
| institution | Kabale University |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-85fee5bc70a14e61ae89f349174459ab2025-08-24T05:11:23ZengElsevierBrain Research Bulletin1873-27472025-10-0123011151810.1016/j.brainresbull.2025.111518Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviorsCheng-Lin Lu0Jing Ren1Wei Wang2Liang-Yu Chen3Xiao-Ying Lian4Xiong Cao5Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Corresponding author.Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaDepartment of Psychology and Behavior, Guangdong Sanjiu Brain Hospital, Institute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, Guangdong, ChinaKey Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaKey Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, ChinaMicrobiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China; Institute for Brain Science and Intelligence, Zhujiang Hospital, Southern Medical University, Guangzhou, China; Corresponding author at: Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.Stress exposure is associated with the development of anxiety disorders, and astrocytes have emerged as critical mediators of stress responses and anxiety pathogenesis. While astrocytic dysfunction has been implicated in these processes, the specific molecular mechanisms remain elusive. In this study, we demonstrate a crucial role for astrocytic glucocorticoid receptors (GRs) in the ventral hippocampus (vHPC) in modulating anxiety-like behaviors. We found that chronic restraint stress specifically reduced the GR expression in the vHPC, with no significant changes observed in the amygdala or dorsal hippocampus. Consistent with this finding, chronic corticosterone administration was found to induce anxiety-like behaviors in mice, accompanied by a significant reduction in the GR expression in the vHPC. The GR reduction, while prominent and functionally significant in astrocytes, is not exclusive to them in the vHPC under these stress conditions. Targeted deletion of GRs in astrocytes resulted in the development of anxiety-like behaviors in mice. Notably, selective ablation of astrocytic GRs specifically within the vHPC region produced similar behavioral phenotypes. RNA sequencing analysis of the vHPC from astrocytic GR-depletion mice identified potential molecular mechanisms underlying the pathomechanisms of astrocytic GRs in anxiety. These findings establish a novel pathway through which astrocytic GRs in the vHPC regulate anxiety-like behaviors, providing new insights into the neurobiological basis of stress-related anxiety disorders and identifying potential therapeutic targets.http://www.sciencedirect.com/science/article/pii/S0361923025003302StressAnxietyAstrocyteGlucocorticoid receptorsHippocampus |
| spellingShingle | Cheng-Lin Lu Jing Ren Wei Wang Liang-Yu Chen Xiao-Ying Lian Xiong Cao Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors Brain Research Bulletin Stress Anxiety Astrocyte Glucocorticoid receptors Hippocampus |
| title | Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors |
| title_full | Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors |
| title_fullStr | Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors |
| title_full_unstemmed | Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors |
| title_short | Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors |
| title_sort | astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety like behaviors |
| topic | Stress Anxiety Astrocyte Glucocorticoid receptors Hippocampus |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025003302 |
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