1. Upregulated Serotonin Causes Sexually Dimorphic Changes in Oxytocin Cell Counts:
A deeper look at OXT neurons through the DHS model
Rachel Harris, Amanda M.K. Madden and Susan L. Zup, Ph.D.
University of Massachusetts at Boston, Department of Psychology, Boston MA
02125Introduction
• Oxytocin: A nonapeptide hormone and neurotransmitter
synthesized in the paraventricular (PVN) and supraoptic
nuclei of the hypthalamus. Thought to be important for
social bonding.
• Autism Spectrum Disorders are characterized as
developmental disorders that involve social impairment,
communications difficulties, and repetitive and
stereotyped behaviors
• The DHS model: Elevated levels of prenatal serotonin
(5-HT) in mother’s blood lead to down regulation of 5-HT
receptors in infant’s brain, and lower numbers of OXT
cells in PVN, which could be responsible for social
deficits.
• Males are much more susceptible to early
developmental disorders than females.
Methods
• Timed-Pregnant Sprague-Dawley dams,then
pups, were injected s.c. with saline or 5-HT
agonist, 5-methoxytryptamine (5-MT) at a dose of
1mg/kg
• At DOB and P2 pups were injected with either
OIL or TP (testosterone proprionate)
• Immunocytochemistry Antibody: anti-OXT [1:15k]
(Millipore JBC1778243)
E12-E22:
5MT/SAL
DOB:
TP/OIL &
5MT/SAL
P2: TP/OIL &
5MT/SAL
P3-P16:
5MT/SAL
P18: Sac
n=13
Future Directions
Based on these findings we are planning on
running an immunofluorescence double label for 5-
HT1A and OXT. The trends from this study and
previous data suggest changes in both 5-HT and
OXT, so we would like to see if there is any
colocalization of 5-HT receptors and OXT cells.
Below are pictures of a pilot study double label ICC
of a P18 male PVN (at 40x and 10x).
References•Carter, C. "Sex Differences in Oxytocin and Vasopressin: Implications for Autism Spectrum Disorders?" Behavioural Brain Research 176.1 (2007): 170-86. Print.
• Dakin, C. L., C. A. Wilson, C. W. Coen, and D. C. Davies. "Neonatal Stimulation of 5-HT2 Receptors Reduces Androgen Receptor Expression in the Rat Anteroventral
Periventricular Nucleus and Sexually Dimorphic Preoptic Area." European Journal of Neuroscience 27 (2008): 2473-480. Print.
• Whitaker-Azmitia, Patricia M. "Behavioral and Cellular Consequences of Increasing Serotonergic Activity during Brain Development: A Role in Autism?" International
Journal of Developmental Neuroscience 23.1 (2005): 75-83. Print.
• Zup, Susan L., and Nancy G. Forger. "Sexual Differentiation, Hormones and." Encyclopedia of the Human Brain 4 (2002): 323-40. Print.
Aknowledgments
• This work was funded in part by a Retired Faculty of Umass Boston Research Award
• To learn more about our lab please visit: https://sites.google.com/site/zuplab/
OXT cells in the PVN
5MT + OIL treated male (10x) 5MT + OIL treated female (10x)
• The preliminary observations show the possible formation of a
few trends.
• 5MT seemed to raise the number of OXT cells, and males
appeared to have more OXT cells than females, while
hypermasculinizing males and masculinizing females showed a
trend toward lower OXT cell counts than normal.
Sex Difference
0
20
40
60
80
100
120
140
Control 5MT TP 5MT + TP
Treatment Group
OXT Neurons in PVN
Male
Female
Summary
• 5MT treated males were expected to have the
lowest OXT counts, the data trends showed a
reverse of this
• 5MT treatment appeared to have possibly raised
levels of OXT cells.
• If these trends hold true in a larger study it may
elucidate something about 5-HT, OXT, and
testosterone fluctuation differences in males and
females at this particular stage in neural
development.
• Due to low n these findings are not statistically
significant, but show interesting trends that should
be investigated with further research.