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.
Dr. Weinberg’s research is supported by grants from the US National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism, NeuroDevNet (Networks of Centres of Excellence of Canada), and the Canadian Foundation for Fetal Alcohol Research. |
- Holman PJ, Ellis L, Morgan E, Weinberg J. (2018). Prenatal alcohol exposure disrupts male adolescent social behavior and oxytocin receptor binding in rodents.Hormones and Behavior. 105:115-127.
- Neuenschwander R, Hookenson K, Brain U, Brunau RE, Devlin AM, Weinberg J, Diamond A, Oberlander TF. (2018). Children’s stress regulation mediates the association between prenatal maternal mood and child executive functions for boys, but not girls. Development and Psychopoathology. 30(3):953-969.
- Lam VYY, Raineki C, Ellis L, Yu W, Weinberg J. (2018). Interactive effects of prenatal alcohol exposure and chronic stress in adulthood on anxiety-like behavior and central stress-related receptor mRNA expression: Sex- and time-dependent effects. Psychoneuroendocrinology. 97:8-19.
- Bodnar TS, Raineki C, Wertelecki W, Yevtushok L, Plotka L, Zymak-Zakutnya N, Honerkamp-Smith G, Wells A, Rolland M, Woodward TS, Coles CD, Kable JA, Chambers CD, Weinberg J, CIFASD. (2018). Altered maternal immune networks are associated with adverse child neurodevelopment: Impact of alcohol consumption during pregnancy. Brain, Behavior, and Immunity. 73:205-215.
- Lam VYY, Raineki C, Takeuchi LE, Ellis L, Woodward TS, Weinberg J. (2018). Chronic stress alters behavior in the forced swim test and underlying neural activity in animals exposed to alcohol prenatally: Sex- and time-dependent effects.Frontiers in Behavioral Neuroscience. 12:42.
- Petrelli B, Weinberg J, Hicks GG. (2018). Effects of prenatal alcohol exposure (PAE): Insights into FASD using PAE mouse models. Biochemistry and Cell Biology. 96(2): 131-147.
- Lussier AA, Morin AM, MacIsaac JL, Salmon J, Weinberg J, Reynolds JN, Pavlidis P, Chudley AE, Kobor MS. (2018). DNA methylation as a predictor of fetal alcohol spectrum disorder. Clinical Epigenetics. 10:5.
- Raineki C, Ellis L, Weinberg J. (2018). Impact of adolescent stress on the expression of stress-related receptors in the hippocampus of animals exposed to alcohol prenatally. 28:201–216.
- Raineki C, Bodnar TS, Holman PJ, Baglot SL, Lan N, Weinberg J. (2017). Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure. Brain, Behavior, and Immunity. 66:210-220.
- Oberle E, McLachlan K, Catherine NLA, Brain U, Schonert-Reichl KA, Weinberg J, Oberlander TF. (2017). Afternoon cortisol provides a link between self-regulated anger and peer-reported aggression in typically developing children in the school context.Developmental Psychobiology. 59(6): 688–695.
- Bodnar TS, Taves MD, Lavigne KM, Woodward TS, Soma KK, Weinberg J. (2017). Differential activation of endocrine-immune networks by arthritis challenge: Insights from colony-specific responses.Scientific Reports. 7(698):1–14.
- Lussier A, Weinberg J, Kobor MS. (2017). Epigenetics studies of fetal alcohol spectrum disorder: where are we now? 9(3):91–311.
- Cameron CA, McKay S, Susman EJ, Wynne-Edwards K, Wright JM, Weinberg J. (2017). Cortisol stress response variability in early adolescence: Attachment, affect and sex. Journal of Youth and Adolescence. 46:104-20.
- Lan N, Chiu MPY, Ellis L, Weinberg J. (2017). Prenatal alcohol exposure and prenatal stress differentially alter glucocorticoid signaling in the placenta and fetal brain. 342:167-79.
- Chau CMY, Cepeda IL, Devlin AM, Weinberg J, Grunau RE. (2017). The Val66Met brain-derived neurotrophic factor gene variant interacts with early pain exposure to predict cortisol dysregulation in 7-year-old children born very preterm: Implications for cognition. Neuroscience. 342:188-99.
- Sliwowska JH, Comeau WL, Bodnar TS, Ellis L, Weinberg J. (2016). Prenatal alcohol exposure and pair feeding differentially impact puberty and reproductive development in female rats: Role of the kisspeptin system. Alcoholism: Clinical and Experimental Research. 40(11):2368-76.
- Raineki C, Chew L, Mok P, Ellis L, Weinberg J. (2016). Short- and long-term effects of stress during adolescence on emotionality and HPA function of animals exposed to alcohol prenatally. 74:13-23.
- Hill LA, Bodnar, TS, Weinberg J, Hammond, GL. (2016). Corticosteroid-binding globulin is a biomarker of inflammation onset and severity in female rats. Endocrinol. 230(2):215-25.
- Bodnar TS, Hill LA, Weinberg J. (2016). Evidence for an immune signature of prenatal alcohol exposure in female rats. Brain, Behavior, and Immunity. 58:130-41.
- Weinberg J. (2016). Commentary: Linking cortical and subcortical developmental trajectories to behavioral deficits in a mouse model of prenatal alcohol exposure. Alcoholism: Clinical and Experimental Research. 40(3):448-50.
- Lan N, Hellemens KG, Ellis L, Weinberg J. (2015). Exposure to chronic mild stress differentially alters corticotropin-releasing hormone and arginine vasopressin mRNA expression in the stress-responsive neurocircuitry of male and female rats prenatally exposed to alcohol. Alcoholism: Clinical and Experimental Research. 39(12):2414-21.
- Bodnar TS, Hill LA, Taves MD, Yu W, Soma KK, Hammond GL, Weinberg J. (2015). Colony specific differences in endocrine and immune responses to an inflammatory challenge in female Sprague-Dawley rats. Endocrinology. 156(12):4604-17.
- Ngai YF, Sulistyoningrum DC, O’Neill R, Innis SM, Weinberg J, Devlin AM. (2015). Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology. 304(4):613-22.
- Lussier AA, Stepien KA, Weinberg J, Kobor MS. (2015). Prenatal alcohol exposure alters gene expression in the rat brain: Experimental design and bioinformatic analysis of microarray data. Data in Brief. 4:239-52.
- Workman J, Raineki C, Weinberg J, Galea LAM. (2015). Alcohol and pregnancy: effects on maternal care, HPAaxis function, and hippocampal neurogenesis in adult females. 57:37-50.
- Comeau WL, Lee K, Anderson K, Weinberg J. (2015). Prenatal alcohol exposure and adolescent stressincrease sensitivity to stress and gonadal hormone influences on cognition in adult female rats. Physiology and Behavior. 148:157-65.
- Uban K, Comeau W, Bodnar T, Yu W, Weinberg J, Galea LAM. (2015). Amphetamine sensitization and crosssensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats. 232(10):1705-16.
- Lussier AA, Stepien KA, Neumann SM, Pavlidas P, Kobor MS, Weinberg J. (2015). Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain. Alcoholism: Clinical and Experimental Research. 39(2):251-261.
- Brummelte S, Chau C, Cepeda I, Deganhardt A, Weinberg J, Synnes A, Grunau RE. (2015). Cortisol levels in former preterm children at school age are predicted by neonatal procedural pain-related stress. 51:151-163.
- Wagner S, Cepeda I, Kreiger D, Maggi S, D’Angiulli A, Weinberg J, Grunau RE. (2015). Higher cortisol associated with poorer executive functioning in preschool children: The role of parenting stress, parent coping and quality of daycare. Child Neuropsychology. 22(7):853-69.
- Sliwowska JH, Bodnar TS, Weinberg J. (2014) Prenatal alcohol exposure alters response of kisspeptin-ir neurons to estradiol and progesterone in adult female rats. Alcohol: Clin Exp Res. 38:2780-2789.
- Comeau WL, Winstanley CA, Weinberg J. (2014) Prenatal alcohol exposure and adolescent stress: Unmasking persistent attentional deficits in rats. Eur J Neurosci. 40(7):3078-95. Epub 2014 Jul 25.
- Mackinnon McQuarrie, MA Siegel LS, Perry NE, Weinberg, J. (2014) Reactivity to stress and the cognitive componenets of math disability in grade 1 children. J Learn Disabil. 47:349-365.
- Raineki C, Hellemans KGC, Bodnar T, Lavigne KM, Ellis L, Woodward TS, Weinberg J. (2014) Neurocircuitry underlying stress and emotional regulation in animals prenatally exposed to alcohol and subjected to chronic mild stress in adulthood. Front Endocrinol (Lausanne). 13:5:5. eCollection 2014.
- Sliwowska JH, Song HJ, Bodnar T, Weinberg J. (2014) Prenatal alcohol exposure results in long-term serotonin neuron deficits in female rats: modulatory role of ovarian steroids. Alcohol Clin Exp Res. 38:152-160.
- Grunau RE, Cepeda IL, Chau CMY, Brummelte S, Weinberg J, Lavoie P, Ladd M, Hirschfeld AF, Russell E, Koren G, Van Uum S, Brant R, Turvey SE. (2013) Neonatal pain-related stress and NFKBIA genotype are associated with altered cortisol levels in preterm boys at school age. PLoS ONE. 8: e73926.
- Uban KA, Comeau W, Ellis L, Galea LAM, Weinberg J. (2013) Plasticity of basal HPA and dopamine systems is altered differentially in males and females by prenatal alcohol exposure and chronic variable stress. Psychoneuroendocrinology. 38:1953-1966.
- Gover A, Chau V, Miller SP, Brant R, McFadden DEl, Poskitt KJ, Synnes Al, Weinberg J, Grunau RE. (2013) Prenatal and postnatal inflammation in relation to cortisol levels in preterm infants at 18 months corrected age. J Perinatology. 33:647-651.
- Lan N, Vogl W, Weinberg J. (2013) Prenatal ethanol exposure delays the onset of spermatogenesis in the rat. Alcohol Clin Exp Res.37:1074-1081. CPS collaboration.
- Vaghri Z, Guhn M, Weinberg J, Grunau RE, Yu W, Hertzman C. (2013) Hair cortisol reflects socio-economic factors and hair zinc in pre-schoolers. Pychoneuroendocrinology. 38:331-340. UBC collaboration.
- Zhang X, Lan N, Bach P, Nordstokke D, Yu W, Ellis L, Meadows GG, Weinberg J. (2012) Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats. Brain Behav. Immun. 26:439-50. International collaboration
- Gover A, Brummelte S, Synnes AR, Miller SP, Brant R, Weinberg J, Grunau RE. (2012) A single course of antenatal steroids did not alter resting cortisol in very preterm infants to 18 months corrected age. Acta Paediatr 101:604-608. UBC collaboration.
- Hill MN, Hellemans KGC, Verma P, Gorzalka BB, Weinberg J. (2012) Neurobiology of chronic mild stress: Parallels to major depression. Neurosci Biobehav Rev. 36:2085-2117.
- D’Angiulli, A, Weinberg J, Oberlander T, Grunau RE, Hertzman C, Maggi S. (2012) Frontal EEG correlates of attentional processes, cortisol and emotional states in adolescent children from lower and higher family socioeconomic status. Frontiers in Human Neuroscience. 6:306. National collaboration
- Brummelte S, Grunau RE, Zaidman-Zait A, Weinberg J, Nordstokke D, Cepeda I. (2011) Cortisol levels in relation to maternal interaction and child internalizing behavior in preterm and full term children at 18 months corrected age. Dev Psychobiol. 53: 184-195. International collaboration.
- Butts KA, Weinberg J, Young AH, Phillips AG. (2011) Glucocorticoid receptors in the prefrontal cortex regulate stress-evoked dopamine efflux and aspects of executive function. Proc Natl Acad Sci U S A 108:18459-18464.
- Scher A, Hall WA, Zaidman-Zait A, Weinberg J. (2010) Sleep quality, cortisol levels, and behavioral regulation in toddlers. Psychobiol. 52:44-53. International collaboration.
- Verma P, Hellemans KGC, Choi F, Yu W, Weinberg J. (2010) Circadian phase and sex effects on depressive/anxiety-like behaviors and HPA axis responses to acute stress. Behav. 99:276-285.
- Hellemans KG, Verma P, Yoon E, Yu WK, Young AH, Weinberg J. (2010) Prenatal alcohol exposure and chronic mild stress differentially alter depressive- and anxiety-like behaviors in male and female offspring. Alcohol Clin Exp Res. 34:633–645.
- Hellemans KGC, Sliwowska JH, Verma P, Weinberg J. (2010) Prenatal alcohol exposure: Fetal programming and later life vulnerability to stress, depression and anxiety disorders. Neurosci Biobehav Rev. 34:791–807.
- Oberlander TF, Jacobson SW, Weinberg J, Grunau RE, Molteno CD, Jacobson JL. (2010). Prenatal alcohol exposure alters biobehavioral reactivity to pain in newborns. Alcohol Clin Exp. Res 34:1-12. International collaboration.
- Haley DW, Grunau RE, Weinberg J, Keidar A, Oberlander TF. (2010) 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.
- Grunau RE, Tu MT, Whitfield MF, Oberlander TF, Weinberg J, Yu W, Thiessen P, Gosse G, Scheifele D. (2010) 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.
- Sliwowska JH, Barker JM, Barha CK, Lan N, Weinberg J, Galea LAM. (2010) Stress-induced suppression of hippocampal neurogenesis in adult male rats is altered by prenatal ethanol exposure. Stress. 13:301-313.
- Uban KA, Sliwowska JH, Lieblich S, Ellis LI, Yu W, Weinberg J, Galea LAM. (2010) 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. 58: 835–843.
- Maken DS, Weinberg J, Cool DR, Hennessy MB. (2010) 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. 124:600-809. International collaboration.
- Stern JM, Weinberg J, Hennessy MB. (2010) From Freud to a modern understanding of behavioral, physiological, and brain development. Dev Psychobiol. 52:609-615. International collaboration.
- Lan N, Hellemans KG, Ellis L, Viau V, Weinberg J.(2009) Role of testosterone in mediating prenatal ethanol effects on hypothalamic-pituitary-adrenal activity in male rats. Psychoneuroendocrinology. 34(9):1314-28.
- Lan N, Yamashita F, Halpert AG, Sliwowska JH, Viau V, Weinberg J.(2009) Effects of prenatal ethanol exposure on hypothalamic-pituitary-adrenal function across the estrous cycle. Clin. Exp. Res. 33:1075-1088.
- Zhang X, Yu M, Yu Wl, Weinberg J, Shapiro J, McElwee KJ. (2009) Development of alopecia areata is associated with higher central and peripheral hypothalamic-pituitary-adrenal tone in the skin graft induced C3H/HeJ mouse model. Investigative Dermatology. 129:1527-1538.
Further publications can be found here.
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