My laboratory is concerned with three areas of research.  First, we focus on the biochemical regulation of sleep.  We described the somnogenic actions of many cytokines.  We showed that interleukin-1 and tumor necrosis factor are involved in physiological sleep regulation.  Further we have an independent project demonstrating the involvement of growth hormone releasing hormone in sleep regulation.  For each of these substances we showed that their mRNA and protein levels vary in brain with the sleep-wake cycle and are affected by sleep deprivation.  We showed that these substances increase non-rapid eye movement sleep (NREMS).  Conversely, if they are inhibited sleep is inhibited and the sleep rebound after sleep deprivation is also blocked.  Mice lacking IL1 or TNF receptors and animals underexpressing GHRH or the GHRH receptor sleep less than normal.  We have also examined many substances related to these somnogens with the goal of developing our knowledge of the biochemical network regulating sleep.

 

Our second interest deals with sleep and infectious diseases.  Bacterial, protozoan, fungal and viral infectious agents greatly alter sleep.  In the case of bacteria we determined the molecular steps responsible.  For example, with gram-positive bacteria, bacterial peptidoglycan (from cell walls) is digested by macrophages, releasing somnogenic muramyl peptides (these are the monomeric building blocks of bacterial cell walls).  Muramyl peptides in turn induce enhanced production of cytokines which in turn affect sleep.  Currently our efforts are focused 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 my laboratory is with sleep function and brain organization as it applies to sleep.  In short, we hypothesized that neuronal groups are the organizational level at which sleep is initiated.  Much recent experimental data support this idea.  For instance, individual cortical columns such as somatosensory barrels alternate between functional states, one of which is usually associated with organism sleep and which is induced by TNF.  We are currently testing the hypothesis that sleep serves a synaptic plasticity function by examination of molecular events associated with synaptic reorganization and whether sleep affects those events.  For example, rats given a whisker cut on one side of the face change several molecular markers of synaptic plasticity in the contralateral somatosensory cortex, e.g. GAD 67, and NGF.  The direction of the change was dependent upon the nature of the ongoing synaptic reorganization.

Obál Jr., F. and J.M. Krueger.  Humoral mechanisms of sleep.  2005.  In:  The Physiological Nature of Sleep.  P.L. Parmeggiani and R. Velluti (eds.); Imperial College Press; pp. 23-44.

Yasuda, T., H. Yoshida, F. Garcia-Garcia, D. Kay, and J.M. Krueger.  2005.  Interleukin-1b has a role in cerebral cortical state dependent electroencephalographic slow-wave activity.  Sleep  28:177-184.

Garcia-Garcia, F., S. Ponce, R. Brown, V. Cussen, and J.M. Krueger.  2005.  Sleep disturbances in the rotenone-animal model of Parkinson Disease.  Brain Res. 1042: 160-168.

Tang, C., M.J. Sula, S. Bohnet. A. Rehman, P. Taishi and J.M. Krueger.  2005.  Interleukin-1b induces CREB-binding protein (CBP) mRNA in brain and the sequencing of rat CBP.  Mol. Brain Res. 137: 213-222.

Krueger, J.M.  Mechanisms underlying the central effects of cytokines.  2005.  In:  Neuroimmune Mechanisms and Chronic Fatigue Syndrome.  NIH Publication No. 04-5497, pp. 63-70.

Alt, J.A., S. Bohnet, P. Taishi, D. Duricka, F. Obál Jr., T. Traynor, J.A. Majde and J.M. Krueger.  2005.  Influenza virus-induced glucocorticoid and hypothalamic cytokine mRNA responses in dwarf Lit/Lit mice.  Brain Behav. Immun.  (published)

Churchill, L., K. Yasuda, T. Yasuda, K. Blindheim, M. Falter, F. Garcia-Garcia, and J.M. Krueger.  2005.  Cortical application of tumor necrosis factor a induces asymmetry in Fos- and interleukin-1b immunoreactive cells within the corticothalamic projection.  Brain Res.  1055: 15-24.

De, A., J.M. Krueger, and S.M. Simasko.  2005.  Expression and release of glutamate-induced TNFa in cultured hypothalamic cells.  Brain Res.  1053: 54-61.

Yasuda, T., K. Yasuda, R. Brown and J.M. Krueger.  2005.  State-dependent effects of the light/dark cycle on the somatosensory and the visual cortex EEG in rats.  Am. J. Physiol.  289: R1083-R1089.

Obál Jr., F., F. Garcia-Garcia, B. Kacsóh, P. Taishi, S. Bohnet, N.D. Horseman, and J.M. Krueger.  2005.  REM sleep is reduced in prolactin deficient mice.  J. Neurosci. 25: 10282-10289.

Majde, J.A. and J.M. Krueger.  2005.  Links between the innate immune system and sleep.  J. Allergy Clin. Immunol. 116: 1188-1198.

Krueger, J.M. and J.A. Majde.  2006.  Sleep and the immune response.  In:  A Comprehensive Handbook of Sleep Medicine.  T.L. Lee-Chiong (ed.); John Wiley & Sons, Inc.: Hoboken, NJ; pp. 767-772.

Traynor, T.R., J.A. Majde, S.G. Bohnet and J.M. Krueger.  2006.  Sleep and body temperature responses in an acute viral infection model are altered in interferon type I receptor-deficient mice.  Brain Beh. Immunity.  20: 290-299.

Kushikata, T., J. Fang, and J.M. Krueger.  2006.  Platelet activating factor and its metabolite promote sleep in rabbits.  Neurosci. Lett. 394: 233-238.

Alfoldi, P., L. Kapás, E. Szentirmai, P. Taishi, J. Gardi, Z. Peterfi, B. Kacsóh, and J.M. Krueger.  2006.  The somatotropic axis in sleep and thermo regulation.  J. Thermal Biol. 31: 30-39.

Szentirmai, E., I. Hajdu, F. Obál Jr. and J.M. Krueger.  2006.  Ghrelin-induced sleep responses in ad libitum fed and food restricted rats.  Brain Res.  1088: 131-140. 

Davis, C.J., P.C. Meighan, P. Taishi, J.M. Krueger, J.W. Harding, and J.W. Wright.  2006.  REM sleep deprivation attenuates actin-binding protein cortactin: a link between sleep and hippocampal plasticity.  Neurosci. Lett. 400; 191-196. 

Szentirmai, E., and J.M. Krueger.  Central administration of neuropeptides Y induces wakefulness in rats.  Am. J. Physiol.  (In press)

Krueger, J.M., J.A. Majde, and D.M. Rector.  Cytokines in immune function and sleep regulation.  Handbook of Clinical Neurology.  (In press)

Peterfi Z, Obál F Jr, Taishi P, Gardi J, Kacsóh B, Unterman T, Krueger JM.  Sleep in spontaneous dwarf rats.  Brain Res. (In press) 

Szentirmai E, Krueger JM.  Obestatin promotes sleep in rats.  Neurosci. Lett. (In press)