Monday, May 6, 2024
5/6/2024
PROJECT SUMMARY Becoming a mother is often associated with a unique sense of joy, serenity, and personal fulfillment. A tremendous number of pregnant and postpartum women cannot reach these positive states, though, because they struggle with high levels of life stress. High pregnancy stress degrades women’s later ability to sensitively care for their infants, and in very severe cases contributes to infant neglect and abuse. In addition, elevated stress during pregnancy is one of the most reliable and strongest predictors of maternal depression and anxiety, which afflict 10-15% of the four million pregnant and recently parturient women in the U.S. each year. There is a dearth of knowledge about the specific neural mechanisms through which stress contributes to maternal depression, anxiety, and poor infant caregiving. Without such knowledge, it is virtually impossible to know how to best intervene or treat women who are at the highest risk. The long-term goal of this line of basic research is to better understand how stress during pregnancy derails postpartum behavior by affecting interactions between the stress-signaling neuropeptide, corticotropin releasing factor (CRF), and the neurotransmitter, serotonin (5-HT). The objective of this R21 exploratory/developmental project is to use a laboratory rat model of motherhood to begin testing the hypothesis that female reproduction generates normative changes in CRF receptors in the midbrain dorsal raphe nucleus (i.e., the source of most forebrain 5- HT), and that these changes are derailed by pregnancy stress. I further hypothesize that the normative changes across reproduction in CRF receptors in the DR protect mothers against the negative consequences of stress on their affective and caregiving behaviors. The proposed multi-method research employs a variety of tools to answer our questions (qRT-PCR, receptor autoradiography, dual-label in situ hybridization, slice electrophysiology, viral vector-mediated gene up/downregulation, detailed behavior analysis) and is innovative because it the first to study how stressed and unstressed female reproduction affect CRF receptors site- specifically in the serotonergic dorsal raphe, and more broadly to provide critical information about the neurochemistry underlying stress’ impact on the female brain and behavior. This important basic research is highly significant because our results have the potential to improve strategies for intervention and treatment of the millions of women and their infants negatively affected by pregnancy stress each year.
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