The overall objective of the proposed studies is to understand mechanisms by which prenatal alcohol exposure can lead to lasting immune deficits. Compelling evidence has indicated that the central nervous system utilizes neuroendocrinologic and autonomic neural pathways to modulate immune responses to immunogenic challenges. The proposed hypothesis is that exposure to alcohol in utero alters brain responsiveness to cytokine- mediated immune signals and, thus, changes the course of normal immune responses.
The specific aims are: first, to characterize effects of prenatal alcohol exposure on brain responsiveness to antigenic challenges; and second, to compare the cerebral responses to immune activation with those elicited by cytokines (e.g. interleukin-1). The subjects, young-adult rats exposed to prenatal alcohol or the appropriate pair-fed controls, will be treated with antigens, interleukin- 1, or the respective vehicles. At various times post-treatment, brain responsiveness to the treatments will be assessed by the activity of: (1) central noradrenergic innervation of discrete brain regions; (2) sympathetic neural projections to lymphoid organs (""""""""sympatho-lymphoid axis""""""""), and (3) the pituitary-adrenocortical humoral axis. Activity of cerebral and sympathetic noradrenergic neurons will be determined by norepinephrine metabolism in the target region. The functional date of the pituitary-adrenal axis will be evaluated by plasma concentrations of adrenocorticotropic hormone and corticosterone. The neurochemical and endocrinologic changes will be correlated with the immune response to the various treatments. The proposed studies will advance our understanding of mechanisms by which prenatal alcohol exposure alters communication between the immune and central nervous system, that may compromise the well-being of the host.
