Research in the Weinberg laboratory is focused on the investigation of how early life experiences alter brain and biological development. We have developed novel rodent models to examine brain-behavior relationships from prenatal life through adulthood. We also collaborate with Drs Grunau, Oberlander and colleagues to examine effects of early life experiences on human development. Overall, we are interested in how interactions between psychosocial and physiological events occurring early in development can produce long-term changes in hormonal, immune and behavioral function, and significantly alter vulnerability or increase resilience to diseases later in life.
A. Rodent models of early life experiences
Fetal Alcohol Spectrum Disorder (FASD) describes the set of birth defects occurring in children born to women chronically consuming high levels of alcohol, and is one of the leading known causes of mental retardation in the Western world. Our animal model reproduces many of the characteristic somatic and functional deficits of human prenatal alcohol exposure. We utilize a broad multi-disciplinary approach to investigate mechanisms underlying prenatal alcohol (ethanol) effects on neuroendocrine and neuroimmune function. We have shown that in adulthood, animals prenatally exposed to ethanol show hyperresponsiveness to stressors, and marked changes in central regulation of hypothalamic-pituitary-adrenal (HPA) or stress axis activity under both basal and stress conditions. Furthermore, sex differences in the effects of ethanol on patterns of HPA responsiveness are often observed, suggesting a role for the gonadal steroids in mediating prenatal ethanol effects on HPA function. Using an animal model of adjuvant-induced arthritis, our data also demonstrate marked ethanol-induced alterations in neuroimmune function, particularly in response to immune challenges and stress (collaborators, Michael Kobor, Gary Meadows [Washington State University]). Finally, we are examining the hypothesis that epigenetic mechanisms may underlie the neuroendocrine and neuroimmune changes observed (collaborators, Sheila Innis, Angela Devlin).
B. Collaborative studies on infant development
Collaborative (Ruth Grunau and colleagues) projects are investigating the long-term consequences of early pain and medication (sedatives and analgesics) exposure on neurobehavioral development. In the neonatal intensive care unit (NICU), infants born at very low (VLGA, ≤32 wk) or extremely low (ELGA, ≤28 wk) post-conceptional age are exposed to prolonged stress and pain related to repeated procedures. Our research begins to address possible mechanisms mediating the effects of early pain and medication exposure on specific aspects of biobehavioral function. Overall, this research is the first to demonstrate that programming of the HPA axis occurs in preterm infants. Studies with Oberlander and colleagues have been examining basal HPA regulation and stress responsiveness in infants with prenatal exposure to serotonin reuptake inhibitors (SRIs). The findings from these studies suggest an early “programming” effect of antenatal maternal mood, prenatal SRI exposure and postnatal maternal care giving on the HPA system, and have potentially important implications for understanding possible long-term effect of maternal depression and SRI treatment.
