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James M. Krueger, Ph.D.
Dr. James M. Krueger is Professor of Veterinary Medicine at Washington State University. He received his B.S. degree from the University of Wisconsin and was awarded a Ph.D. from the University of Pennsylvania. He also did postdoctoral studies at Harvard Medical School.
Dr. Krueger has presented at 206 symposiums and seminars. He has published 259 manuscripts; 260 abstracts; and 16 nonscientific papers. Dr. Krueger's research is funded through the National Institutes of Health. His research team is interested in the biochemical regulation of sleep. They were the first to describe the somnogenic actions of cytokines. They developed most of the evidence showing that interleukin-1 and tumor necrosis factor are involved in physiological sleep regulation. Dr. Krueger's team has an independent project demonstrating the involvement of growth hormone releasing hormone (GHRH) in sleep regulation. Thus, for each of these substances mRNA and protein levels vary in the brain with the sleep-wake cycle and are affected by sleep deprivation. If any one of these substances is administered, increases in nonrapid eye movement sleep (NREMS) occur. Conversely, if they are inhibited, sleep is inhibited and sleep rebound after sleep deprivation also is blocked. Mice lacking IL1 or TNF receptors sleep less than normal, and animals under-expressing GHRH or the GHRH receptor in brain sleep less than normal. Dr. Krueger's team also has examined many substances related to these somnogens with the goal of developing knowledge of the biochemical cascade regulating sleep.
Dr. Krueger's second interest is with the relationships between sleep and infectious diseases. His team has described sleep changes induced by bacterial, protozoan, fungal and viral infectious agents. In the case of bacteria, they have worked out the molecular steps responsible for their induction of sleep. For example, bacterial peptidoglycan is digested by macrophages, releasing somnogenic muramyl peptides. Muramyl peptides in turn induce enhanced production of cytokines, which in turn affect sleep. Currently, Dr. Krueger's team is focusing their efforts on the mechanisms involved in influenza virus-induced sleep. In this case, viral double-stranded RNA, released from infected cells, seems responsible for initiating the sleep cascade.
A third interest of Dr. Krueger's laboratory is with sleep function and brain organization as it applies to sleep. In short, they hypothesized that neuronal groups are the minimal organizational level at which sleep occurs. Much recent experimental data support this idea. His laboratory also hypothesized that sleep serves a synaptic plasticity function. They are currently testing this hypothesis by examining molecular events associated with synaptic reorganization and whether sleep affects those events. For example, they recently showed that in rats given a whisker cut on one side of the face, there is a change of several molecular markers of synaptic plasticity in the contralateral somatosensory cortex (e.g., GAD 67, and NGF). The direction of the change was dependent on the nature of the ongoing synaptic reorganization.
March 2002
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