The focus of the proposal is to understand the role of critical developmental periods which, when altered, lead to growth failure using the rat as an animal model. Efforts are concentrated on two stages of the rat's development, i.e., the first two weeks of life, when activation and termination of stress can be altered in opposite directions, depending on the timing of stressors and on the post-weaning period when the rat is no longer dependent upon maternal care for survival. Focus is placed upon the hypothalamus, hippocampus, and pituitary because these structures are thought to exert important neural and endocrine control upon the LHPA and the growth hormone (GH) axes. It is proposed to: 1) examine the consequences of early stress (maternal deprivation at specified times in life) on growth parameters; 2) examine if the individual differences in stress responsiveness resulting from maternal deprivation alter the expression of molecules linked to a functional GH axis during development; 3) attempt to revert the long-term negative effects of maternal deprivation by blocking the LHPA response to stress during early life with a CRH antagonist; and 4) explore psychopathology in families of children being seen for growth evaluation.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Freund, Lisa S
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Schools of Medicine
Ann Arbor
United States
Zip Code
Vázquez, Delia M; Neal Jr, Charles R; Patel, Paresh D et al. (2012) Regulation of corticoid and serotonin receptor brain system following early life exposure of glucocorticoids: long term implications for the neurobiology of mood. Psychoneuroendocrinology 37:421-37
Vazquez, Delia M; Bailey, Charles; Dent, Gersham W et al. (2006) Brain corticotropin-releasing hormone (CRH) circuits in the developing rat: effect of maternal deprivation. Brain Res 1121:83-94
Lopez, Nestor L; Vazquez, Delia M; Olson, Sheryl L (2004) An integrative approach to the neurophysiological substrates of social withdrawal and aggression. Dev Psychopathol 16:69-93
Neal Jr, Charles R; Weidemann, Gabrielle; Kabbaj, Mohamed et al. (2004) Effect of neonatal dexamethasone exposure on growth and neurological development in the adult rat. Am J Physiol Regul Integr Comp Physiol 287:R375-85
Neal Jr, Charles R; VanderBeek, Brian L; Vazquez, Delia M et al. (2003) Dexamethasone exposure during the neonatal period alters ORL1 mRNA expression in the hypothalamic paraventricular nucleus and hippocampus of the adult rat. Brain Res Dev Brain Res 146:15-24
Vazquez, Delia M; Eskandari, Ramin; Phelka, Andrew et al. (2003) Impact of maternal deprivation on brain corticotropin-releasing hormone circuits: prevention of CRH receptor-2 mRNA changes by desipramine treatment. Neuropsychopharmacology 28:898-909
Flagel, Shelly B; Vazquez, Delia M; Watson Jr, Stanley J et al. (2002) Effects of tapering neonatal dexamethasone on rat growth, neurodevelopment, and stress response. Am J Physiol Regul Integr Comp Physiol 282:R55-63