The Leuner Lab conducts preclinical research to address issues/questions that are specific to the female brain and women’s brain health:
MATERNAL BRAIN AND BEHAVIOR
Neuroimmune alterations in the peripartum brain
There are robust changes in the maternal immune system which are necessary to support a successful pregnancy. To date, these immune changes have been observed in the periphery but a fundamental gap exists in our understanding of whether immune changes extend to the brain to influence behavior. We are investigating how microglia, the primary innate immune cells of the brain, are altered across the peripartum period and following gestational stress. We are also examining their role in maternal care and how they may contribute to stress-induced depressive-like behavior during the postpartum period.
Exposure to gestational stress as a translational model for postpartum depression
Becoming a mother is usually regarded as one of life’s most emotionally positive and rewarding experiences but for a significant number of women, the postpartum period can instead be a difficult time accompanied by mental illness. Indeed, recent analyses indicate that at least 15% of new mothers worldwide each year are affected by postpartum depression (PPD). Although PPD is common and known to be detrimental for maternal well-being and to adversely affect mother-infant interactions, the neurobiology of PPD is understudied and thus poorly understood. To address this issue, my laboratory has developed a rodent model of postpartum depression based on a well-known risk factor, chronic exposure to stress during pregnancy. We have found that postpartum rats exposed to chronic gestational stress exhibit increased depressive-like behavior as well as several other behavioral changes which reflect some of the symptoms seen in depressed mothers including impaired maternal care, cognitive dysfunction and reward-related deficits. Our goal is to understand how stress affects brain circuits that underlie these behaviors in order to elucidate potential mechanisms that may contribute to maternal depression.
The impact of opioids on the maternal brain and behavior
7% of pregnant women use opioids, constituting a major public health problem for mothers and their children. Most research focuses on how opioid exposure in utero affects child neurodevelopment; Yet pregnancy is also a time of significant change in the mother’s brain, allowing for the onset of mothering. The dynamic nature of the pregnant mother’s brain also renders it vulnerable to insults that could derail caregiving abilities, precipitate postpartum depression, or drive drug relapse. We are using a preclinical rodent model of pregnancy opioid exposure, alongside chronic stress, which is high in individuals who use opioids, in order to characterize the impact on: 1) maternal caregiving; 2) anxiety/depression; and 3) maternal brain systems that may underlie behavioral outcomes and which may represent targets for therapeutic intervention.
HORMONAL CONTRACEPTIVES
Effects of hormonal contraceptives on the adolescent brain
Millions of individuals take hormonal contraceptives (HC) often starting at adolescence when ovarian hormones have important effects on brain maturation, especially the the prefrontal cortex (PFC). Yet, there is a fundamental lack of information about the consequences of hormonal alterations with adolescent HC use on PFC development. Considering that HC usage among adolescents has been associated with greater depression risk in adulthood, we aim to understand how HC influence mood regulating brain regions like the PFC.
The Leuner Lab collaborates with Dr. Kathryn Lenz and her laboratory on the above projects.
Approach
We use a variety of techniques in our research including:
Behavioral assays to assess cognitive, emotional and social behaviors including attentional set shifting, elevated plus maze, open field, forced swim test, sucrose preference test, social interaction test, conditioned place preference, maternal behavior
Stereotaxic surgery to provide pharmacological treatments into specific brain regions
Neuroanatomical techniques such as Golgi and DiI labeling for analysis of neuronal morphology, tract tracing, immunohistochemical and immunoflurorescent staining, brightfield and confocal microscopy, IMARIS
Molecular biology and biochemical analyses such as qPCR, Western blot and ELISA
Funding
The lab has been funded by grants from:
National Science Foundation
National Institute of Mental Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Brain and Behavior Research Foundation
The Ohio State University Chronic Brain Injury Program
The Ohio State Addiction Innovation Initiative