دورية أكاديمية
Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior.
| العنوان: | Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior. |
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| المؤلفون: | Fitzsimons CP; Department of Medical Pharmacology, Leiden University Medical Center/Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands., van Hooijdonk LW, Schouten M, Zalachoras I, Brinks V, Zheng T, Schouten TG, Saaltink DJ, Dijkmans T, Steindler DA, Verhaagen J, Verbeek FJ, Lucassen PJ, de Kloet ER, Meijer OC, Karst H, Joels M, Oitzl MS, Vreugdenhil E |
| المصدر: | Molecular psychiatry [Mol Psychiatry] 2013 Sep; Vol. 18 (9), pp. 993-1005. Date of Electronic Publication: 2012 Aug 28. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996- |
| مواضيع طبية MeSH: | Hippocampus/*cytology , Motivation/*genetics , Neurogenesis/*genetics , Neurons/*physiology , Receptors, Glucocorticoid/*deficiency, Animals ; Cell Movement/genetics ; Conditioning, Classical/physiology ; Corticosterone/metabolism ; Dendrites/metabolism ; Dendrites/ultrastructure ; Dendritic Spines/metabolism ; Dendritic Spines/ultrastructure ; Fear ; Genetic Vectors/physiology ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; In Vitro Techniques ; Memory Disorders/genetics ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Nerve Tissue Proteins/metabolism ; Neurons/ultrastructure ; Presynaptic Terminals/metabolism ; RNA, Small Interfering/metabolism ; Radioimmunoassay |
| مستخلص: | Glucocorticoids (GCs) secreted after stress reduce adult hippocampal neurogenesis, a process that has been implicated in cognitive aspects of psychopathology, amongst others. Yet, the exact role of the GC receptor (GR), a key mediator of GC action, in regulating adult neurogenesis is largely unknown. Here, we show that GR knockdown, selectively in newborn cells of the hippocampal neurogenic niche, accelerates their neuronal differentiation and migration. Strikingly, GR knockdown induced ectopic positioning of a subset of the new granule cells, altered their dendritic complexity and increased their number of mature dendritic spines and mossy fiber boutons. Consistent with the increase in synaptic contacts, cells with GR knockdown exhibit increased basal excitability parallel to impaired contextual freezing during fear conditioning. Together, our data demonstrate a key role for the GR in newborn hippocampal cells in mediating their synaptic connectivity and structural as well as functional integration into mature hippocampal circuits involved in fear memory consolidation. |
| المشرفين على المادة: | 0 (Nerve Tissue Proteins) 0 (RNA, Small Interfering) 0 (Receptors, Glucocorticoid) 0 (enhanced green fluorescent protein) 147336-22-9 (Green Fluorescent Proteins) W980KJ009P (Corticosterone) |
| تواريخ الأحداث: | Date Created: 20120829 Date Completed: 20140325 Latest Revision: 20141120 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1038/mp.2012.123 |
| PMID: | 22925833 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1476-5578 |
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| DOI: | 10.1038/mp.2012.123 |