Document Detail

Effects of neonatal treatment with valproic acid on vasopressin immunoreactivity and olfactory behaviour in mice.
MedLine Citation:
PMID:  21793947     Owner:  NLM     Status:  MEDLINE    
Recent findings demonstrate that epigenetic modifications are required for the sexual differentiation of the brain. For example, neonatal administration of the histone deacetylase inhibitor, valproic acid, blocks masculinisation of cell number in the principal nucleus of the bed nucleus of the stria terminalis (BNST). In the present study, we examined the effects of valproic acid on neurochemistry and behaviour, focusing on traits that are sexually dimorphic and linked to the BNST. Newborn mice were treated with saline or valproic acid and the effect on vasopressin immunoreactivity and olfactory preference behaviour was examined in adulthood. As expected, males had more vasopressin immunoreactive fibres than females in the lateral septum and medial dorsal thalamus, which are two projection sites of BNST vasopressin neurones. Neonatal valproic acid increased vasopressin fibre density specifically in females in the lateral septum, thereby reducing the sex difference, and increased vasopressin fibres in both sexes in the medial dorsal thalamus. The effects were not specific to BNST vasopressin projections, however, because valproic acid also significantly increased vasopressin immunoreactivity in the anterior hypothalamic area in both sexes. Subtle sex-specific effects of neonatal valproic acid treatment were observed on olfactory behaviour. As predicted, males showed a preference for investigating female-soiled bedding, whereas females showed a preference for male-soiled bedding. Valproic acid did not significantly alter olfactory preference, per se, although it increased the number of visits females made to female-soiled bedding and the overall time females spent investigating soiled versus clean bedding. Taken together, these results suggest that a transient disruption of histone deacetylation at birth does not have generalised effects on sexual differentiation, although it does produce lasting effects on brain neurochemistry and behaviour.
E K Murray; M M Varnum; J L Fernandez; G J de Vries; N G Forger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  23     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-28     Completed Date:  2012-01-18     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  906-14     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.
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MeSH Terms
Animals, Newborn
Mice, Inbred C57BL
Valproic Acid / pharmacology*
Vasopressins / metabolism*
Grant Support
R01 MH068482/MH/NIMH NIH HHS; R01 MH068482-08/MH/NIMH NIH HHS; R01-MH068482/MH/NIMH NIH HHS
Reg. No./Substance:
11000-17-2/Vasopressins; 614OI1Z5WI/Valproic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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