The postpartum period is accompanied by dramatic clianges in hormones, including increased glucocorticoid and decreased estrogen levels. In virgin rodents, high glucocorticoid and low estrogen levels have been associated with diminished dendritic architecture and fewer dendritic spines, sites of excitatory synapses, in the medial prefrontal cortex (mPFC). This hormonal environment has also been shown to negatively impact behaviors mediated by the mPFC, by impairing cognitive function and enhancing anxiety. Despite the known detrimental effects of high glucocorticoid and low estrogen levels, mothers with this hormonal profile exhibit attenuated anxiety. In addition, research conducted during the K99 phase has shown that dendritic spine density is increased in the mPFC of mother rats and that this effect coincides with improved attention and behavioral flexibility, functions that depend on the mPFC. However, the factors that shield the maternal mPFC from the potentially damaging postpartum hormonal milieu remain unknown. The neuropeptide oxytocin has been shown to buffer stress hormone effects on the brain and behavior and may play a role in protecting mPFC structure and function during motherhood. To investigate this, manipulations of oxytocin receptors, cognitive, anxiety, and maternal behavioral assays and measures of structural plasticity will be employed. The results of these studies will inform us ofthe neural and behavioral alterations associated with motherhood and the role that oxytocin may play in these changes. This work serves as the independent portion of the K99/R00 award and will provide the foundation for a research program focused on elucidating the mechanisms of brain resilience.

Public Health Relevance

For many women, motherhood is a rewarding experience. Yet, an estimated 15% of new mothers suffer from depression/anxiety. Dramatic postpartum hormonal changes may contribute to this by predisposing some to react negatively to the demands of parenting. Since the mPFC and OT have been linked to maternal care and mood disorders, understanding motherhood and OT induced alterations in mPFC structure and function may uncover mechanisms underlying susceptibility and resilience to postpartum mental illness.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Transition Award (R00)
Project #
5R00MH084148-05
Application #
8427294
Study Section
Special Emphasis Panel (NSS)
Program Officer
Simmons, Janine M
Project Start
2008-09-02
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2013
Total Cost
$233,593
Indirect Cost
$80,417
Name
Ohio State University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Galea, L A M; Leuner, B; Slattery, D A (2014) Hippocampal plasticity during the peripartum period: influence of sex steroids, stress and ageing. J Neuroendocrinol 26:641-8
Leuner, Benedetta; Fredericks, Peter J; Nealer, Connor et al. (2014) Chronic gestational stress leads to depressive-like behavior and compromises medial prefrontal cortex structure and function during the postpartum period. PLoS One 9:e89912
Sabihi, Sara; Durosko, Nicole E; Dong, Shirley M et al. (2014) Oxytocin in the prelimbic medial prefrontal cortex reduces anxiety-like behavior in female and male rats. Psychoneuroendocrinology 45:31-42