Document Detail

Synapse loss from chronically elevated glucocorticoids: relationship to neuropil volume and cell number in hippocampal area CA3.
MedLine Citation:
PMID:  16871536     Owner:  NLM     Status:  MEDLINE    
Individuals with clinical disorders associated with elevated plasma glucocorticoids, such as major depressive disorder and Cushing's syndrome, are reported to have smaller hippocampal volume. To understand how the hippocampus responds at the cellular and subcellular levels to glucocorticoids and how such changes are related to volume measures, we have undertaken a comprehensive study of glucocorticoid effects on hippocampal CA3 volume and identified elements in the neuropil including astrocytic volume and cell and synapse number and size. Male Sprague-Dawley rats were injected with corticosterone (40 mg/kg), the primary glucocorticoid in rodents, or vehicle for 60 days. The CA3 was further subdivided so that the two-thirds of CA3 (nearest the dentate gyrus) previously shown to be vulnerable to corticosterone could be analyzed as two separate subfields. Corticosterone had no effect on neuropil volume or glial volume in the proximal subfield but caused a strong tendency for astrocytic processes to make up a larger proportion of the tissue and for volume of tissue made of constituents other than glial cells (primarily neuronal processes) to be smaller in the middle subfield. Within the neuropil, there were no cellular or subcellular profiles that indicated degeneration, suggesting that corticosterone does not cause prolonged damage. Corticosterone did not reduce cell number or cell or nonperforated synapse size but did cause a pronounced loss of synapses. This loss occurred in both subfields and, therefore, was independent of volume loss. Together, the findings suggest that volume measures can underestimate corticosterone effects on neural structure.
Despina A Tata; Veronica A Marciano; Brenda J Anderson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of comparative neurology     Volume:  498     ISSN:  0021-9967     ISO Abbreviation:  J. Comp. Neurol.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-01     Completed Date:  2006-10-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0406041     Medline TA:  J Comp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  363-74     Citation Subset:  IM    
Department of Psychology, State University of New York at Stony Brook, Stony Brook, New York 11790-2500, USA.
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MeSH Terms
Astrocytes / metabolism,  pathology
Atrophy / chemically induced,  physiopathology*
Cell Count
Cell Death / drug effects,  physiology
Chronic Disease
Depressive Disorder, Major / complications,  physiopathology
Disease Models, Animal
Gliosis / chemically induced,  physiopathology
Glucocorticoids / adverse effects,  metabolism*
Hippocampus / metabolism,  pathology*,  physiopathology
Nerve Degeneration / chemically induced,  physiopathology*
Neurons / drug effects,  metabolism,  pathology*
Neuropil / drug effects,  metabolism,  pathology*
Pituitary ACTH Hypersecretion / complications,  physiopathology
Pyramidal Cells / drug effects,  metabolism,  pathology
Rats, Sprague-Dawley
Stress, Physiological / complications,  physiopathology
Synapses / drug effects,  metabolism,  pathology*
Up-Regulation / physiology
Grant Support
Reg. No./Substance:

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