1. Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex.
- Author
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Anderson RM, Glanz RM, Johnson SB, Miller MM, Romig-Martin SA, and Radley JJ
- Subjects
- Animals, Cell Size, Corticosterone administration & dosage, Dendritic Spines pathology, Dose-Response Relationship, Drug, Drug Implants, Fluorescent Dyes, Imaging, Three-Dimensional, Male, Microscopy, Confocal, Microscopy, Fluorescence, Models, Animal, Neuronal Plasticity physiology, Prefrontal Cortex pathology, Pyramidal Cells pathology, Radioimmunoassay, Rats, Sprague-Dawley, Stress, Psychological metabolism, Stress, Psychological pathology, Corticosterone metabolism, Dendritic Spines metabolism, Prefrontal Cortex metabolism, Pyramidal Cells metabolism
- Abstract
The stress-responsive hypothalamo-pituitary-adrenal (HPA) axis plays a central role in promoting adaptations acutely, whereas adverse effects on physiology and behavior following chronic challenges may result from overactivity of this system. Elevations in glucocorticoids, the end-products of HPA activation, play roles in adaptive and maladaptive processes by targeting cognate receptors throughout neurons in limbic cortical networks to alter synaptic functioning. Because previous work has shown that chronic stress leads to functionally relevant regressive alterations in dendritic spine shape and number in pyramidal neurons in the medial prefrontal cortex (mPFC), this study examines the capacity of sustained increases in circulating corticosterone (B) alone to alter dendritic spine morphology and density in this region. Subcutaneous B pellets were implanted in rats to provide continuous exposure to levels approximating the circadian mean or peak of the steroid for 1, 2, or 3 weeks. Pyramidal neurons in the prelimbic area of the mPFC were selected for intracellular fluorescent dye filling, followed by high-resolution three-dimensional imaging and analysis of dendritic arborization and spine morphometry. Two or more weeks of B exposure decreased dendritic spine volume in the mPFC, whereas higher dose exposure of the steroid resulted in apical dendritic retraction and spine loss in the same cell population, with thin spine subtypes showing the greatest degree of attrition. Finally, these structural alterations were noted to persist following a 3-week washout period and corresponding restoration of circadian HPA rhythmicity. These studies suggest that prolonged disruptions in adrenocortical functioning may be sufficient to induce enduring regressive structural and functional alterations in the mPFC. J. Comp. Neurol. 524:3729-3746, 2016. © 2016 Wiley Periodicals, Inc., Competing Interests: The authors declare no competing financial interests., (© 2016 Wiley Periodicals, Inc.)
- Published
- 2016
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