Document Detail

Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor.
MedLine Citation:
PMID:  18445216     Owner:  NLM     Status:  MEDLINE    
In the present study, we established and characterized an animal model of vulnerability to repeated stress. We found that control Sprague-Dawley (SD) rats showed a gradual decrease in the HPA axis response following 14 days of repeated restraint stress, whereas Fischer 344 (F344) rats did not show such HPA axis habituation. Similar habituation was observed in the expression of c-fos mRNA, corticotropin-releasing hormone hnRNA, and phospho-CREB and phospho-ERK proteins in the hypothalamic paraventricular nucleus (PVN) of SD rats, but not in the F344 rats. In addition, repeatedly restrained F344 rats exhibited decreased cell proliferation in the dentate gyrus of the hippocampus and increased anxiety-related behaviours, while repeatedly restrained SD rats exhibited a selective enhancement of hippocampal cell proliferation in the ventral area. Moreover, we found a lower expression of glucocorticoid receptor (GR) protein, but not mRNA, in the PVN of F344 rats compared to SD rats. We also identified that microRNA (miR)-18a inhibited translation of GR mRNA in cultured neuronal cells and that increased expression of miR-18a in the PVN was observed in F344 rats compared with SD rats. These strain differences in GR protein levels were not found in the hippocampus and prefrontal cortex, and the expression of miR-18a was much lower in these brain regions than in the PVN. Our results suggest that F344 rats could be a useful animal model for studying vulnerability to repeated stress, and that miR-18a-mediated down-regulation of GR translation may be an important factor to be considered in susceptibility to stress-related disorders.
Shusaku Uchida; Akira Nishida; Kumiko Hara; Toshiki Kamemoto; Masatomo Suetsugi; Michiko Fujimoto; Toshio Watanuki; Yusuke Wakabayashi; Koji Otsuki; Bruce S McEwen; Yoshifumi Watanabe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The European journal of neuroscience     Volume:  27     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-30     Completed Date:  2008-07-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  France    
Other Details:
Languages:  eng     Pagination:  2250-61     Citation Subset:  IM    
Division of Neuropsychiatry, Department of Neuroscience, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan.
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MeSH Terms
Anxiety / etiology
Blotting, Northern
Blotting, Western
Body Weight
Brain / physiology*
Cell Proliferation
Corticosterone / blood
Corticotropin-Releasing Hormone / metabolism
Cyclic AMP Response Element-Binding Protein / metabolism
Disease Models, Animal
Extracellular Signal-Regulated MAP Kinases / metabolism
Genes, fos / physiology
Habituation, Psychophysiologic / physiology*
Hypothalamo-Hypophyseal System / physiology
In Situ Hybridization
MicroRNAs / genetics,  metabolism*
Pituitary-Adrenal System / physiology
RNA, Messenger / analysis
Rats, Inbred F344
Rats, Sprague-Dawley
Receptors, Glucocorticoid / biosynthesis*,  genetics
Receptors, Mineralocorticoid / biosynthesis
Restraint, Physical
Reverse Transcriptase Polymerase Chain Reaction
Stress, Psychological / physiopathology*
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/MicroRNAs; 0/RNA, Messenger; 0/Receptors, Glucocorticoid; 0/Receptors, Mineralocorticoid; 50-22-6/Corticosterone; 9015-71-8/Corticotropin-Releasing Hormone; EC Signal-Regulated MAP Kinases

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