Current Research:
The brain responds to pertubation, irrespective of the nature of the stimulus. Brain responses to pertubation almost invariably include changes in behavior, which may be interpreted in a functional sense as designed to return systems to acceptable physiologic status. One behavior, sleep, is of particular interest because we do not know what sleep does for the brain. The critical nature of sleep is evidenced by how we “feel” when we do not get enough, and by the fact that prolonged sleep deprivation is fatal. Our research focuses on stressor-induced alterations in arousal state. Elucidating mechanisms by which stressors alter arousal state may shed some light on the fundamental question of what sleep does for the brain. We focus on two types of stressors, those that are psychological in nature (ie, no tissue injury, trauma, or physical insult), and infection. These classes of stressors overlap to a large extent in anatomical and chemical substrates activated, yet behavioral responses diverge; psychological stressors generally increase wakefulness and arousal, whereas infection increases sleep. To understand how different stressors that activate many of the same brain systems result in different behavioral outcomes, we focus on interactions in brain between neurotransmitters (corticotropin-releasing hormone [CRH], serotonin [5-HT]) and immune-active cytokines (interleukin [IL]-1). We have determined, for example that: blocking CRH actions in brain induces IL-1, which in turn increases sleep; blockade of 5-HT2 receptors interferes with changes in sleep normally induced by IL-1; that components of HIV are capable of altering sleep and upregulating IL-1 expression in brain; and that mice lacking a functional gene for an inhibitory cytokine, IL-10, not only sleep differently than intact animals in response to immune challenge, but also have altered sleep in the absence of any challenge. Collectively, results of these studies indicate that interactions in brain between neurotransmitters and immune-active substances are functionally relevant to the regulation of complex behavior. Whether the changes in sleep aid in recovery from challenge remains to be determined.
Representative Publications:
Morrow JD, Opp MR. "Diurnal Variation of Lipopolysaccharide-Induced Alterations in Sleep and Body Temperature of Interleukin-6-Deficient Mice." Brain, Behavior, and Immunity, (in press).
Morrow JD, Opp MR. "Sleep-Wake Behavior and Responses of Interleukin-6-Deficient Mice to Sleep Deprivation. Brain, Behavior, and Immunity, (in press).
Imeri LP, Ceccarelli P, Mariotti M, Manfridi A, Opp MR, and Mancia M. Sleep, but not febrile responses of Fisher 344 rats to immune challenge are affected by aging. Brain, Behavior, and Immunity 18:399-404, 2004.
Chang FC, Opp MR. "A Corticotropin-Releasing Hormone Antisense Oligodeoxynucleotide Reduces Spontaneous Waking in the Rat." Regulatory Peptides, 117:43-52, 2004.
Manfridi A, Brambilla D, Bianchi S, Mariotti M, Opp MR, and Imeri L. "Interleukin ?1Beta Enhances Non-Rapid Eye Movement Sleep when Microinjected into the Dorsal Raphe Nucleus and Inhibits Serotonergic Neurons In Vitro." European Journal of Neuroscience, 18: 1041-1049, 2003.
Gemma C, Imeri L, Opp MR. "Serotonergic Activation Stimulates the Pituitary-Adrenal Axis and Alters Interleukin-1 mRNA Expression in Rat Brain." Psychoneuroendocrinology, 28: 875-884, 2003.
Opp MR, Toth LA. Neural-immune interactions in the regulation of sleep. Frontiers in Bioscience 8: D768-D779, 2003.
Hogan D, Morrow JD, Smith EM, Opp MR. "Interleukin-6 Alters Sleep of Rats." Journal of Neuroimmunology, 137:59-66, 2003.
Chang FC Opp MR. "Role of Corticotropin-Releasing Hormone in Stressor-Induced Alterations of Sleep in Rat." American Journal of Physiology, 283: R400-R407, 2002.
Rose M, Sanford A, Thomas C, Opp MR. "Factors Altering the Sleep of Burned Children." Sleep, 24:45-51, 2001.
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