An investigation into the impact of pregnancy and stress on neuroimmune function: Are there potential links to postpartum depression?
Date
2015
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Postpartum depression is a specific type of major depression outlined by the National Institute of Mental Health that affects approximately 10-15% of mothers. While many have attributed postpartum depression to a dramatic change in hormone levels throughout pregnancy and the immediate postpartum period, the exact causes of postpartum depression are not well-understood. Pregnancy induces a striking increase in the levels of circulating hormones including progesterone, estrogen, prolactin and oxytocin. In addition, pregnancy induces significant changes in the peripheral immune system in order to foster the development of the growing fetus and to prevent it from being "attacked" by the mother's immune system. It is also well-known that changes in immune function, specifically within the brain, have been linked to several neuropsychiatric disorders including depression. Despite the fact that pregnancy is associated with dramatic changes in peripheral immune function, no one has ever examined whether pregnancy produces similar changes in immune function within the brain. Therefore, we hypothesize that functional changes in the immune system associated with pregnancy and parturition may increase the risk for developing postpartum depression. Microglia are the immune cells of the brain. They produce both pro- and anti-inflammatory cytokines in response to various insults such as infection, stress, and injury. Using real-time PCR analysis of gene expression within the brain, we identified significant changes in the expression of microglial activation markers and pro-inflammatory molecules within the medial prefrontal cortex (mPFC) and the hippocampus of pregnant and postpartum rats. Separate cohorts of pregnant and non-pregnant rats were exposed to either forced swimming stress during the last week of gestation or an injection of an immunogenic compound, lipopolysaccharide (LPS), one day prior to parturition. These challenges induced differential changes of two inflammatory cytokines, Il-1? and Il-6, in the mPFC after birth. Both stress and pregnancy caused depressive-like anhedonia and increased anxiety as measured using sucrose preference testing and performance on an Elevated Plus Maze, respectively. Thus, our data show novel findings of neuroimmune changes and depressive-like behaviors induced by pregnancy alone. Additionally, stress and immune activation interact with pregnancy resulting in unique neuroimmune changes and depressive-like behavioral outcomes.