Journal article
Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex
Journal of comparative neurology (1911), Vol.524(18), pp.3729-3746
12/15/2016
DOI: 10.1002/cne.24027
PMCID: PMC5063662
PMID: 27113541
Abstract
ABSTRACT\nThe 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.\nUsing high‐resolution confocal laser scanning microscopy, we show that prolonged elevations in corticosterone induce persistent alterations in dendritic spine morphology and decreased density in rat medial prefrontal cortex. This darkfield image shows layer 2/3 prefrontal pyramidal neurons selected for intracellular dye‐filling with Lucifer yellow (cyan).
Details
- Title: Subtitle
- Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex
- Creators
- Rachel M Anderson - University of IowaRyan M Glanz - University of IowaShane B Johnson - University of IowaMary M Miller - University of IowaSara A Romig‐Martin - University of IowaJason J Radley - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of comparative neurology (1911), Vol.524(18), pp.3729-3746
- DOI
- 10.1002/cne.24027
- PMID
- 27113541
- PMCID
- PMC5063662
- NLM abbreviation
- J Comp Neurol
- ISSN
- 0021-9967
- eISSN
- 1096-9861
- Number of pages
- 18
- Grant note
- National Institutes of Health (MH‐095972)\nBrain & Behavior Research Foundation National Alliance for Research on Schizophrenia and Depression (to J.J.R.)
- Language
- English
- Date published
- 12/15/2016
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute
- Record Identifier
- 9984070894802771
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