[Abstract Title]. - Society for Neuroscience

Disclosures: B.M. Nugent, None; J.M. Schwarz, None; M.M. McCarthy , None.
Poster
278. Sex Differences I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 278.12/MM5
Topic: E.01.e. Sexual differences
Support: NIH Grant KO2 MH01497
NIH Grant RO1 MH068482
NIH Grant R01 MH47538
Title: Epigenetic control of sexual differentiation of the bed nucleus of the stria terminalis in
mice
Authors: *E. K. MURRAY, A. HIEN, G. J. DE VRIES, N. G. FORGER;
Neurosci & Behavior Program, Univ. Massachusetts, Amherst, Amherst, MA
Abstract: The principal nucleus of the bed nucleus of the stria teminalis (BNSTp) is larger and
contains more cells in male mice than in females. These sex differences arise from a higher rate
of cell death during early postnatal life in females. Perinatal differences in testosterone appear to
create this difference because neonatal testosterone treatment reduces cell death in females to the
level seen in males. There is a delay of about six days between testosterone exposure and the
peak of cell death, indicating that cells somehow „remember‟ whether or not they have been
exposed to high levels of testosterone. This suggests that epigenetic mechanisms control cell
fate. We examined whether histone acetylation, which is typically associated with activation of
gene expression, plays a role in the sexual differentiation of the BNSTp. We manipulated the
balance between histone acetylation and deacetylation by treating animals with the histone
deacetylase inhibitor valproic acid (VPA) at the critical time for sexual differentiation. Males,
females, and females treated neonatally with testosterone were treated with 50mg/kg VPA or
saline on postnatal days 1 and 2. Animals were sacrificed on postnatal day 21 and volume and
cell number of the BNSTp was determined. VPA treatment did not influence volume or cell
number in control females but significantly reduced both of these parameters in males and
testosterone-treated females, thereby eliminating the sex difference. No volume changes were
noted in the suprachiasmatic nucleus, suggesting that the VPA effect was specific to the BNSTp.
These findings suggest that a disruption in histone deacetylation blocks the masculinizing actions
of testosterone in the BNSTp.