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REPEATED STRESS ALTERS DENDRITIC SPINE MORPHOLOGY IN THE RAT MEDIAL PREFRONTAL CORTEX
Journal article   Peer reviewed

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 H Morrison, Susan L Wearne and Patrick R Hof
Journal of comparative neurology (1911), Vol.507(1), pp.1141-1150
03/01/2008
DOI: 10.1002/cne.21588
PMCID: PMC2796421
PMID: 18157834
url
https://www.ncbi.nlm.nih.gov/pmc/articles/2796421View
Open Access

Abstract

Anatomical alterations in the medial prefrontal cortex (mPFC) are associated with hypothalamo-pituitary 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 which rapidly digitizes, reconstructs 3-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 layers 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 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.
stress plasticity dendritic spine morphometry prefrontal cortex

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