Our research focuses how brain development is shaped by interactions between the nervous, endocrine and immune systems. We aim to understand the mechanisms that govern normal brain development and lifelong behavior, and how various factors can disrupt this normal development and increase risk for neurodevelopmental disorders, such as autism.
- Innate immune cells and sex differences in normal brain development
Hormones act early in life to produce sex differences in brain architecture, biochemistry, and physiology and to program sex differences in behavior. In this project, we are studying how hormones influence the function and signaling of innate immune cells in the brain, including microglia and mast cells, in brain development. Our current focus is on the role immune cells play in developmental neurogenesis, cell death, and synaptic patterning and related changes in social, affective, and reproductive behaviors throughout life.
- Effects of prenatal stress and inflammation on development of brain and behavior
Prenatal stress and prenatal exposure to inflammation increase risk for many neurodevelopmental disorders, including autism, schizophrenia, ADHD, and bipolar disorder. In this project we seek to determine how maternal stress and/or inflammation during pregnancy acutely alter functioning of the placenta, the developing blood brain barrier and the brain’s immune cells in fetuses during critical periods of brain development. We will correlate changes in fetal tissues to social behavior, impulsivity, hyperactivity, and mood-related changes in later life to determine which fetal changes are predictive of later life behavioral disturbances.
- Neuroimmune function during the peripartum period
In collaboration with Dr. Benedetta Leuner at OSU, we are studying the role of microglia as regulators of brain and behavioral plasticity in females during pregnancy and the postpartum period. We have found robust changes in the neuroimmune environment of the brain over the course of normal pregnancy and extending into the postpartum period. We are now testing whether these changes are necessary for the onset of normal maternal behavior and determining whether hormones of pregnancy are responsible for neuroimmune changes. We are also investigating whether gestational stress, a major risk factor for postpartum depression, perturbs these normal neuroimmune alterations to result in mood-related disturbances and disrupted maternal care in the postpartum period.
We use a variety of techniques to ask the research questions above in rodent models, including:
Neuronatomical techniques: Sterological cell counting, Golgi-cox impregnation and cell reconstruction, histological and immunohistochemical staining, tract tracing, traditional and confocal microscopy.
Molecular biology/biochemical analyses: Western blot, qPCR, enzyme activity assay, hormone and neurotransmitter measurements.
Cell culture: Primary cell culture, in vitro pharmacological manipulation, in vitro phagocytosis assays.
Behavioral manipulation and analysis: Manipulations include drug treatment, survival surgery, perinatal stress exposure, maternal deprivation, perinatal immune or allergic challenge. Assessments include maternal behavior, stress reactivity, anxiety and depression tests, social behavior tests, sexual behavior tests.