Thesis Poster

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 DirectionsBased 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

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Control 5MT TP 5MT + TPTreatment Group

OXT Neurons in PVN

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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.