USU Neuroscience

mpoth@usuhs.mil
 
Ph.D., University of Pittsburgh, 1997
 
Immuno-modulation of the hypothalamo-pituitary-adrenal axis
 
Research Interests
 
The lab focuses on the central pathways involved in the stimulation of the hypothalamo-pituitary-adrenal axis (HPA) by cytokines such as interleukin-1 (IL-1) and other immune system modulators. IL-1 is released from immune cells of macrophage lineage during infectious and inflammatory insults and is an important mediator of peripheral and central components of the acute phase response. Because IL-1 is a large macromolecule that does not cross the blood-brain barrier in significant amounts, critical questions remain as to how IL-1 gains access to the central nervous system, in general, and to stress-related paraventricular (PVH) control systems, in particular. Glucocorticoids, the end products of HPA stimulation are potent inhibitors of immune system function. Understanding this bi-directional communication between the immune system and a neuroendocrine mechanism has implications for autoimmune disorders such as multiple sclerosis.
 
Current Projects
 
The role of perivascular cells in mediating the response to IL-1 or LPS: Using a selective method for ablating perivascular cells (PVCs), I have shown that IL-1 induced Fos within the paraventricular nucleus (PVH) and cyclooxygenase-2 (COX-2) expression within the brain is significantly attenuated in rats without PVCs. This is the first evidence that PVCs are necessary and sufficient for mediating the activation of PVH induced by IL-1. In addition LPS challenge in this paradigm results in increased Fos expression within the PVH and increased COX-2 expression by endothelial cells throughout the brain vasculature. This suggests that PVCs may normally inhibit the response of endothelial cells and at a minimum suggests that there is communication between these two cell types. Ongoing experiments in the lab will focus on the communication between endothelial cells and PVCs and their role in conveying signals across the blood brain barrier and initiating central responses to immune stimuli.
 
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