miRNA Expression Patterns of Neuron Originating Exosomes and Postpartum Depression

Project Summary Postpartum depression (PPD) significantly affects many new mothers, leading to increased mortality and impairing their ability to care for their newborns and their overall well-being. The underlying neurobiological mechanisms of PPD remain unclear, partly due to research limitations focusing on peripheral samples that do not adequately reveal central nervous system (CNS) processes. One promising alternative approach is analyzing the cargo of neuron-derived exosomes (NDEs), which are small, membrane-bound sacs transporting various cargo like proteins, nucleic acids, and lipids throughout the body. The small size of the exosomes allows them to easily pass through the blood-brain barrier. These exosomes, released as part of normal cell physiology, are found in various biofluids like blood serum and contain microRNA (miRNA) as one it primary cargo, which is critical for gene expression regulation. There is substantial evidence linking NDEs in peripheral blood to CNS pathology. For example, NDEs from Alzheimer’s and Parkinson’s patients carry disease-specific proteins, suggesting that their cargo reflects brain pathologies. Studies using rodent models and CNS neuron tracking have confirmed that these exosomes can cross the blood-brain barrier and appear in peripheral blood, further supporting their potential as indicators of brain biology. This research proposal aims to investigate the relationship between PPD and miRNA expression patterns of neuron-derived exosomes. We hypothesize that changes in brain-originating exosome miRNA may reflect alterations in neural pathways linked to PPD. To achieve study aims, we will leverage existing serum samples from a longitudinal study of adult pregnant women. Our study will consist of three groups of women including 25 women with postpartum onset of a major depressive episode (PPD), 25 women with non-pregnancy related major depression disorder (MDD), and 25 women without a history of PPD or MDD (controls). All women were measured across the first, second, and third trimester as well as the postpartum period, for a total of 300 person-time points. Our two aims will 1) characterize miRNA patterns across pregnancy and into the postpartum and 2) compare perinatal NDE miRNA patterns between mood disorder groups and controls. NDE miRNAs identified in study aims will be probed with complementary network-based analyses to identify involved neurobiological pathways. Insights from this study will clarify whether there is scientific merit to proceed to in vivo studies as well as causally informative, longitudinal studies of PPD. This approach promises not only to enhance our understanding of PPD but also to provide broader insights into maternal mental health and the biological basis of this condition.