We aim to decipher mechanisms by which the African trypanosome can cross the blood-brain barrier to cause sleeping sickness, characterized by disrupted sleep pattern with narcolepsy-like sleep episodes. We also aim to study the potential effects of influenza virus, vaccine, or a combination of them on the sleep structure in mice.
Three projects are pursued. One aims to decipher mechanisms by which the African trypanosome can cross the blood-brain barrier to cause sleeping sickness, characterized by disrupted sleep pattern with narcolepsy-like sleep episodes. The immune response to the parasite plays a paradoxical role to promote invasion of the trypanosome into the brain. Another project aims to study the potential effects of influenza virus, vaccine, or a combination of them on the sleep structure in mice.
Previously we have observed that certain influenza virus strains can invade the brain along cranial nerves and in immunodeficient mice infect diencephalic neurons and remain persistent for months after infection. The potential functional effects of such infections on sleep areas are recorded by a wireless NeuroLogger system.
Finally effects of stimulation or inhibition of intracellular signaling pathways on prion formation is studied. We have found that this can have opposite effects.
We are now trying to understand how a balanced state of prion formation may at some point undergo a transition to an irreversible state progressively leading to death of the neuron and the individual. Prion infections have this course of event in common with other neurodegenerative diseases, but since prions are infectious, the phenomenon can be well studied in cell cultures.
H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep-wake regulatory neurons in mice.
Tesoriero C, Codita A, Zhang MD, Cherninsky A, Karlsson H, Grassi-Zucconi G, et al
Proc. Natl. Acad. Sci. U.S.A. 2016 Jan;113(3):E368-77
Tryps and trips: cell trafficking across the 100-year-old blood-brain barrier.
Bentivoglio M, Kristensson K
Trends Neurosci. 2014 Jun;37(6):325-33
Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs.
Rouvinski A, Karniely S, Kounin M, Moussa S, Goldberg MD, Warburg G, et al
J. Cell Biol. 2014 Feb;204(3):423-41
Prion formation correlates with activation of translation-regulating protein 4E-BP and neuronal transcription factor Elk1.
Allard EK, Grujic M, Fisone G, Kristensson K
Neurobiol. Dis. 2013 Oct;58():116-22
Microbes' roadmap to neurons.
Nat. Rev. Neurosci. 2011 Jun;12(6):345-57