Interfaculty Research Cooperation - Decoding Sleep

Sleep-wake disturbances following tick-borne encephalitis (TBE)

Sagittal brain sections of infected rat at day 4 p.i stained with Langat virus antibody
Sagittal brain sections of infected rat at day 4 p.i stained with Langat virus antibody. Viral antigens (LGTV; red) are present in different brain regions including cerebellum (C), midbrain (Mb), hippocampus (Hc), thalamus (Th) and frontal pole (FP).

In viral meningoencephalitis, altered sleep-wake functions, including hypersomnia, disturbances of sleep and impaired sleep quality, are frequently observed. Patients after tick borne encephalitis complain of sleep-wake disturbances and fatigue. The pathophysiological mechanisms causing sleep-wake disorders and/or fatigue in TBE are largely unknown to date. Studies in patients and experimental models show an affinity of TBE virus (TBEV) for the basal ganglia, mesencephalon, diencephalon, medulla oblongata, pons, as well as spinal anterior horn cells. Hence, we speculate, that viral induced local inflammation (acute or chronic), tissue damage or metabolic disturbances in these brain regions following viral invasion cause altered sleeping patterns.

This research project will follow two approaches:

a) In an experimental model using Langat virus as a model organism for TBEV, we will investigate whether the infection cause histopathological changes/damage in thalamus, hypothalamus and mesencephalon and/or induce alteration of sleep-wake regulation and, if yes,  whether the onset and/or severity of sleep dysregulation during or after TBE is a direct result from apoptosis, necrosis or physiological dysfunction of the infected neuronal cells or an indirect consequence of other molecular changes induced by the resulting inflammation. We therefore combine histology, immunofluorescence, inflammatory parameter determination, in vivo electrophysiology, polysomnographic recordings and vigilance states analysis.

b) In a clinical study, we will assess data on sleep-wake disorders in the acute phase and post TBE infection in patients in a prospective as well as retrospective study design using questionnaires, actigraphy, biomarkers analysis and neuroimaging followed by a prospective analysis of damage to the thalamus..

The results of this combined clinical-experimental approach are expected to have implications in our understanding of the link between sleep-wake disturbances and other infectious or inflammatory conditions in the CNS.