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 02125 Introduction • 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 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.

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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

100

120

140

Control 5MT TP 5MT + TPTreatment Group

OXT Neurons in PVN

MaleFemale

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.