Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex

Jason J. Radley, Anne B. Rocher, Alfredo Rodriguez, Douglas B. Ehlenberger, Mark Dammann, Bruce S. Mcewen, John Morrison, Susan L. Wearne, Patrick R. Hof

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

Anatomical alterations in the medial prefrontal cortex (mPFC) are associated with hypothalamopituitary adrenal (HPA) axis dysregulation, altered stress hormone levels, and psychiatric symptoms of stress-related mental illnesses. Functional imaging studies reveal impairment and shrinkage of the mPFC in such conditions, and these findings are paralleled by experimental studies showing dendritic retraction and spine loss following repeated stress in rodents. Here we extend this characterization to how repeated stress affects dendritic spine morphology in mPFC through the utilization of an automated approach that rapidly digitizes, reconstructs three dimensionally, and calculates geometric features of neurons. Rats were perfused after being subjected to 3 weeks of daily restraint stress (6 hours/day), and intracellular injections of Lucifer Yellow were made in layer II/III pyramidal neurons in the dorsal mPFC. To reveal spines in all angles of orientation, deconvolved high-resolution confocal laser scanning microscopy image stacks of dendritic segments were reconstructed and analyzed for spine volume, surface area, and length using a Rayburst-based automated approach (8,091 and 8,987 spines for control and stress, respectively). We found that repeated stress results in an overall decrease in mean dendritic spine volume and surface area, which was most pronounced in the distal portion of apical dendritic fields. Moreover, we observed an overall shift in the population of spines, manifested by a reduction in large spines and an increase in small spines. These results suggest a failure of spines to mature and stabilize following repeated stress and are likely to have major repercussions on function, receptor expression, and synaptic efficacy.

Original languageEnglish (US)
Pages (from-to)1141-1150
Number of pages10
JournalJournal of Comparative Neurology
Volume507
Issue number1
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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Dendritic Spines
Prefrontal Cortex
Spine
Neurotransmitter Receptor
Pyramidal Cells
Confocal Microscopy
Psychiatry
Rodentia
Hormones
Neurons
Injections
Population

Keywords

  • Dendritic spine
  • Morphometry
  • Plasticity
  • Prefrontal cortex
  • Stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Radley, J. J., Rocher, A. B., Rodriguez, A., Ehlenberger, D. B., Dammann, M., Mcewen, B. S., ... Hof, P. R. (2008). Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. Journal of Comparative Neurology, 507(1), 1141-1150. https://doi.org/10.1002/cne.21588

Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. / Radley, Jason J.; Rocher, Anne B.; Rodriguez, Alfredo; Ehlenberger, Douglas B.; Dammann, Mark; Mcewen, Bruce S.; Morrison, John; Wearne, Susan L.; Hof, Patrick R.

In: Journal of Comparative Neurology, Vol. 507, No. 1, 01.03.2008, p. 1141-1150.

Research output: Contribution to journalArticle

Radley, JJ, Rocher, AB, Rodriguez, A, Ehlenberger, DB, Dammann, M, Mcewen, BS, Morrison, J, Wearne, SL & Hof, PR 2008, 'Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex', Journal of Comparative Neurology, vol. 507, no. 1, pp. 1141-1150. https://doi.org/10.1002/cne.21588
Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, Mcewen BS et al. Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. Journal of Comparative Neurology. 2008 Mar 1;507(1):1141-1150. https://doi.org/10.1002/cne.21588
Radley, Jason J. ; Rocher, Anne B. ; Rodriguez, Alfredo ; Ehlenberger, Douglas B. ; Dammann, Mark ; Mcewen, Bruce S. ; Morrison, John ; Wearne, Susan L. ; Hof, Patrick R. / Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. In: Journal of Comparative Neurology. 2008 ; Vol. 507, No. 1. pp. 1141-1150.
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