Depression is often described as a stress-related disorder, as it often occurs in the context of exposure to some form of stress. Indeed, alterations in HPA activity and regulation are one of the most consistently described biological abnormalities in depression and bipolar disorder. Stress can cause remodelling and microdamage in the brain, and can stimulate neuroinflammation. Moreover, significant risk factors for major depressive disorder are associated with increased inflammation;in turn, inflammatory mediators can induce depressive symptoms. In most cases, short-term stress-induced neuroinflammatory activation resolves, and the organism is then resilient in the face of later-life challenges. In the case of an organism with pre-existing vulnerability, such as occurs with PAE, short-term neuroinflammation may fail to resolve, and can progress to a more chronic condition, leaving the organism vulnerable to later life challenge. The present proposal will test the hypothesis that fetal programming of HPA activity by PAE results in altered neuroendocrine- neuroimmune interactions, giving rise to a sensitized, vulnerable organism, with an increased pro- inflammatory bias, that is predisposed to increased responsiveness to stressors or immune challenges later in life, resulting in increased vulnerability to stress-related disorders such as depression and anxiety. This hypothesis will be tested in three Specific Aims: 1) To determine the immediate or short-term effects of PAE and later life stress on depressive-/anxiety-like behavior and behavior mediated by the PFC, as well as markers of stress and neuroimmune function;2) To examine the long-term effects of PAE and stress in adulthood or adolescence on depressive-/anxiety-like behavior and behavior mediated by the PFC, as well as markers of stress and neuroimmune function;and 3) To investigate the efficacy of antidepressant and anti-inflammatory treatments, separately or in combination, in attenuating or normalizing the adverse effects of PAE and later life stress and/or immune challenges on behavioral, brain, HPA and neuroimmune outcomes. Together, the data from these studies will have important implications for the development of novel therapeutic interventions for depression in individuals with FASD.
The present research utilizes our well-established animal model of prenatal alcohol exposure to examine the role of stress and neuroimmune abnormalities in mediating the increased incidence of depression observed in children with FASD. Our data will significantly increase our understanding of the mechanisms underlying the long-term consequences of prenatal alcohol exposure on health and well-being, and will have important imniinatinns fnr the rievelonmfint of novel theranfiittin interventions fnr dfinrfi."?.<=;inn in inriividiials with FASD.
|Bodnar, Tamara S; Hill, Lesley A; Weinberg, Joanne (2016) Evidence for an immune signature of prenatal alcohol exposure in female rats. Brain Behav Immun 58:130-141|
|Raineki, Charlis; Chew, Leanne; Mok, Perry et al. (2016) Short- and long-term effects of stress during adolescence on emotionality and HPA function of animals exposed to alcohol prenatally. Psychoneuroendocrinology 74:13-23|
|Sliwowska, Joanna Helena; Comeau, Wendy L; Bodnar, Tamara S et al. (2016) Prenatal Alcohol Exposure and Pair Feeding Differentially Impact Puberty and Reproductive Development in Female Rats: Role of the Kisspeptin System. Alcohol Clin Exp Res 40:2368-2376|
|Weinberg, Joanne (2016) Commentary: Linking Cortical and Subcortical Developmental Trajectories to Behavioral Deficits in a Mouse Model of Prenatal Alcohol Exposure. Alcohol Clin Exp Res 40:448-50|
|Lan, Ni; Hellemans, Kim G C; Ellis, Linda et al. (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. Alcohol Clin Exp Res 39:2414-21|
|Lussier, Alexandre A; Stepien, Katarzyna A; Neumann, Sarah M et al. (2015) Prenatal alcohol exposure alters steady-state and activated gene expression in the adult rat brain. Alcohol Clin Exp Res 39:251-61|
|Comeau, Wendy L; Lee, Kristen; Anderson, Katie et al. (2015) Prenatal alcohol exposure and adolescent stress increase sensitivity to stress and gonadal hormone influences on cognition in adult female rats. Physiol Behav 148:157-65|
|Workman, Joanna L; Raineki, Charlis; Weinberg, Joanne et al. (2015) Alcohol and pregnancy: Effects on maternal care, HPA axis function, and hippocampal neurogenesis in adult females. Psychoneuroendocrinology 57:37-50|
|Ngai, Ying Fai; Sulistyoningrum, Dian C; O'Neill, Ryan et al. (2015) Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain. Am J Physiol Regul Integr Comp Physiol 309:R613-22|
|Bodnar, Tamara S; Hill, Lesley A; Taves, Matthew D et al. (2015) Colony-Specific Differences in Endocrine and Immune Responses to an Inflammatory Challenge in Female Sprague Dawley Rats. Endocrinology 156:4604-17|
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