CellPhys Faculty - Weinberg

BA (Brown University)
PhD (Stanford University)

Office: 604-822-6214, Lab: 604-822-4554
Email: joannew@interchange.ubc.ca

Research Interests

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.

Recent Publications

Haley, D.W., Grunau, R.E. & Weinberg, J. (2006). Cortisol, contingency learning and memory in preterm and full term infants. Psychoneuroendocrinology 31:108-117.

Redila, V.A., Olson, A.K., Swann, S.E., Mohades, G., Webber, A.J., Weinberg, J. & Christie, B.R. (2006). Hippocampal cell proliferation is reduced following prenatal ethanol exposure but can be rescued with voluntary exercise. Hippocampus 16:305-311.

Lan, N., Yamashita, F., Halpert, A., Ellis, L., Yu, W., Viau, V. & Weinberg, J. (2006). Prenatal ethanol exposure alters the effects of gonadectomy on hypothalamic-pituitary-adrenal activity in male rats. J. Neuroendo. 18:1-13.

Gabriel, K.G., Yu, C.L., Osborn, J.A. & Weinberg, J. (2006). Prenatal ethanol exposure alters sensitivity to the effects of corticotrophin-releasing factor (CRF) on behavior in the elevated plus maze. Psychoneuroendocrinology 31:1046-1056.

Glavas, M.M., Yu, W.K. & Weinberg, J. (2006). Effects of mineralocorticoid and glucocorticoid receptor blockade on hypothalamic-pituitary-adrenal function in rats prenatally exposed to ethanol. Alcohol Clin Exp Res 30:1916-1924.

Kerr, L.R., Andrews, H.N., Strange, K.S., Emerman, J.T. & Weinberg, J. (2006). Temporal factors alter effects of social housing conditions on responses to chemotherapy and hormone levels in a Shionogi mammary tumor model. Psychosom Med 68:966-975.

Hofmann, C.E., Ellis, L., Yu, W.K., & Weinberg, J. (2006). Neuroendocrine responses to 5-HT1a and 5-HT2A/C agonists are differentially altered in female and male rodents prenatally exposed to ethanol. Alcohol. Clin. Exp. Res. 31:345-55.

Grunau, R.E., Haley, D.W., Whitfield, M.F., Weinberg, J., Yu, W. & Thiessen, P. (2007). Altered basal cortisol levels at 3, 6, 8 and 18 months in preterm infants born extremely low gestational age. J. Pediatrics 150:151-156.

Tu M.T., Grunau R., Petrie-Thomas J., Haley. D.W., Weinberg. J. & Whitfield, M.F. (2007). Maternal stress and behavior modulate relationships between neonatal stress, attention and basal cortisol at 8 months in preterm infants. Devel Psychobiol 49:150-164.

Holsti, L., Grunau, R.E. & Weinberg J. (2007). Relationships between adrenocorticotropic hormone and cortisol are altered in preterm infants born at extremely low gestational age. Early Human Devel. 83:341-348.

Glavas, M.M., Ellis, L., Yu, W.K. & Weinberg, J. (2007). Effects of prenatal ethanol exposure on basal limbic-hypothalamic-pituitary-adrenal regulation: Role of corticosterone. Alcohol. Clin. Exp. Res. 31:1598-1610.

Wong, T.P., Howland, J.G., Fox, C.J., Ge, Y., Yu, W., Russell, K.I., Brebner, K., Liu L., Weinberg, J., Christie, B.R., Phillips, A.G. & Wang, Y.T. (2007). Hippocampal long-term depression plays a critical role in stress-induced spatial memory impairment. PNAS 104:11471-11476.

Oberlander, T.F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S. & Devlin, A. (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3:1-9.

Haley, D.W., Grunau, R.E., Oberlander, T.F. & Weinberg, J. (2008). Contingency Learning and reactivity in preterm and full-term infants at 3 months. Infancy 13:570-595.

Sliwowska, J.H., Lan, N., Yamashita, F., Halpert, A.G., Viau, V. & Weinberg, J. (2008). Effects of prenatal ethanol exposure on basal hypothalamic-pituitary-adrenal activity and hippocampal 5HT1A receptor mRNA levels in female rats across the estrous cycle. Psychoneuroendocrinology 33:1111-1123.

Hellemans, K.G.C., Verma, P.V., Yoon, E., Yu, W. & Weinberg, J. (2008). Prenatal alcohol exposure increases vulnerability to stress and anxiety-like disorders in adulthood. Ann. NY Acad. Sci. 1144:154-175.

Oberlander, T.F., Grunau, R., Mayes, L., Riggs, W., Rurak, D., Papsdorf, M., Misri, S. & Weinberg, J. (2008). Hypothalamic-pituitary-adrenal (HPA) axis function in 3 month old infants with prenatal selective serotonin reuptake inhibitor (SRI) antidepressant exposure. Early Human Devel. 84: L689-697.

Weinberg, J., Sliwowska, J.H., Lan, N. & Hellemans, K.G.C. (2008). Prenatal alcohol exposure: Foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome. J Neuroendo. 20:470-488.

Zhang, X., Yu, M., Yu, W.I., Weinberg, J., Shapiro, J. & McElwee, K.J. (2008). 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, in press.

Images

Detection of glucocorticoid mRNA by in situ hybridization.