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.
Weinberg, J., Sliwowska, J.G., Hellemans, K.G.C. Prenatal alcohol exposure: Foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome. J. Neuroendo. 20:470-488, 2008
Haley, D.W., Grunau, R.E., Overlander, T.F., & Weinberg, J. Contingency learning and reactivity in preterm and full-term infants at 3 months. Infancy 13:570-595, 2008.
Oberlander, T.F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, D. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3:1-9., 2008.
Sliwowska, J.H., Lan, N., Yamashita, F., Halpert, A.G., Viau, V., & Weinberg, J. Effects of prenatal ethanol exposure on basal hypothalamic-pituitary-adrenal activity and hippocampal 5HT1a receptor mRNA levels in female rats across the estrous cycle. Psychoneuroendocrinol 33:1111-1123, 2008.
Hellemans, K.G., Verma, P.V., Yoon, E., Hapert, A.G., Viau, V., & Weinberg, J. Prenatal alcohol exposure increases vulnerability to stress and anxiety-like disorders in adulthood. Ann. NY Acad. Sci. 1144:154-175, 2008.
Oberlander, T.F., Grunau, R., Mayes, L., Riggs, W., Rurak, D., Papsdorf, M., Misri, S., & Weinberg, J. Hypothalamic-pituitary-adrenal (HPA) axis function in 3 month old infants with prenatal selective serotonin reuptake inhibitor (SRI) antidepressant exposure. Early Human Development 84: L689-697, 2008.
Zhang, X., Yu, M., Yu, W.l., Weinberg, J., Shapiro, J. & McElwee, K.J. Development of alopecia areata is associated with higher central and peripheral hypothalamic-pituitary-adrenal tone in the skin graft induced C3H/HeJ mouse model. J. Investigative Dermatology 129:1527-1538, 2009.
Lan, N., Yamashita, F., Halpert, A.G., Sliwowska, J.H., Viau, V. & Weinberg, J. Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal function across the estrous cycle. Alcohol. Clin. Exp. Res.33:1075-1088, 2009.
Lan N, Hellemans KG, Ellis L, Viau V, Weinberg J. Role of testosterone in mediating prenatal ethanol effects on hypothalamic-pituitary-adrenal activity in male rats. Psychoneuroendocrinology 34(9):1314-28, 2009.
Scher, A., Hall, W.A., Zaidman-Zait, A., & Weinberg, J. Sleep quality, cortisol levels, and behavioral regulation in toddlers. Dev. Psychobiol. 52:44-53, 2010.
Verma, P., Hellemans, K.G.C., Choi, F., Yu, W., Weinberg, J. Circadian phase and sex effects on depressive/anxiety-like behaviors and HPA axis responses to acute stress. Physiol. Behav.99:276-285, 2010.
Hellemans, K.G., Verma, P., Yoon, E., Yu, W.K., Young, A.H., Weinberg, J. Prenatal alcohol exposure and chronic mild stress differentially alter depressive- and anxiety-like behaviors in male and female offspring. Alcohol Clin Exp Res. 2010. Jan 26 [epub ahead of print].
Oberlander, T.F., Jacobson, S.W., Weinberg, J., Grunau, R.E., Molteno, C.D., Jacobson, J.L. Prenatal alcohol exposure alters biobehavioral reactivity to pain in newborns. Alcohol Clin Exp Res 34:1-12, 2010.
Haley DW, Grunau RE, Weinberg J, Keidar A, Oberlander TF. Physiological correlates of memory recall in infancy: vagal tone, cortisol, and imitation in preterm and full-term infants at 6 months. Infant Behav Dev 33:219-234, 2010.
Grunau RE, Tu MT, Whitfield MF, Oberlander TF, Weinberg J, Yu W, Thiessen P, Gosse G, Scheifele D. Cortisol, behavior, and heart rate reactivity to immunization pain at 4 months corrected age in infants born very preterm. Clin J Pain. 26:698-704, 2010.
Sliwowska, J.H., Barker, J.M., Barha, C.K., Lan, N., Weinberg, J., Galea, L.A.M. Stress-induced suppression of hippocampal neurogenesis in adult male rats is altered by prenatal ethanol exposure. Stress 13:301-313.
Uban, K.A., Sliwowska, J.H., Lieblich, S., Ellis, L.I., Yu, W., Weinberg, J., Galea, L.A.M. Prenatal alcohol exposure reduces the proportion of newly produced neurons and glia in the dentate gyrus of the hippocampus in female rats. Hormones and Behavior, in press.
Brummelte, S. Grunau, R.E., Zaidman-Zait, A., Weinberg, J. Nordstokke, D., Cepeda, I. Cortisol levels in relation to maternal interaction and child internalizing behavior in preterm and full term children at 18 months corrected age. Devel Psychobiol, in press.
Maken DS, Weinberg J, Cool DR, Hennessy MB. An investigation of the effects of maternal separation and novelty on central mechanisms mediating pituitary-adrenal activity in infant guinea pigs (cavia porcellus). Behav Neurosci. 2010 Nov 1. [Epub ahead of print].
Hellemans, K.G., Sliwowska, J.H., Verma, P., Weinberg, J. Prenatal alcohol exposure: Fetal programming and later life vulnerability to stress, depression and anxiety disorders. Neurosci. Biobehav. Rev. 34:791–807, 2010.
Potential graduate students should apply directly to Dr. Weinberg via email with an attached CV.