Early life stress can predispose individuals to a variety of maladies later in life, including behavioral disorders, infectious, autoimmune, and chronic diseases. The basis of this relationship remains to be determined. However, evidence suggests that early life stress permanently alters the """"""""programming"""""""" of stress response causing a """"""""dysregulation"""""""" of immune function. However, the exact mechanisms mediating the adverse effects on immune function and disease susceptibility remain unresolved. Our long-term goal is to understand how prenatal stress (i.e., maternal stress) affects stress responsiveness, immune system function, and susceptibility to pathogens. Our hypothesis is that maternal stress induces long-lasting changes in the stress response, which alters innate and adaptive immunity and therefore inflammatory processes and susceptibility to infectious disease. Understanding the mechanisms by which """"""""programming"""""""" alters the relationship between the stress response and immune system will suggest novel behavioral and pharmacological targets for prevention and intervention of immune system dysfunctions. To test our central hypothesis, we will use pigs from mothers (sows) subjected to a controlled stressor during a specific period of gestation (maternally stressed sows) to produce progeny (pigs) with altered responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS). These pigs will then be used to address the following:
Specific Aim 1. Determine the relationship between activity of the HPA axis, SNS and the acute phase response (APR) of pigs from Control and Maternally Stressed sows during an in vivo lipopolysaccharide (LPS) challenge;
Specific Aim 2. Determine the effect of a fiadrenergic receptor (J3-ADR) antagonist on the APR of pigs from Control and Maternally Stressed sows during an in vivo LPS challenge;
Specific Aim 3. Determine the effect of a ft-ADR agonist on the APR of pigs from Control and Maternally Stressed sows during an in vivo LPS challenge;
Specific Aim 4. Determine the effect of an a-adrenergic receptor (cc-ADR) antagonist on the APR of pigs from Control and Maternally Stressed sows during an in vivo LPS challenge;
and Specific Aim 5. Determine the effect of an a-ADR agonist on the APR of pigs from Control and Maternally Stressed sows during an in vivo LPS challenge. The proposed research is innovative as it will determine to what extent maternal stress impacts specific components of the postnatal stress response and immune system function. Collectively, these outcomes are important as they could lead to the development of targeted pharmacological and behavioral interventions designed to reduce the adverse effects of maternal stress on disease susceptibility
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