What is it about?

Peripheral injection of bacterial lipopolysaccharide (LPS) facilitates 8–10 Hz spike-wave discharges (SWD) characterizing absence epilepsy in WAG/Rij rats. It is unknown however, whether peripherally administered LPS is able to alter the generator areas of epileptic activity at the molecular level. We injected 1 mg/kg dose of LPS intraperitoneally into WAG/Rij rats, recorded the body temperature and EEG, and examined the protein expression changes of the proteome 12 h after injection in the frontoparietal cortex and thalamus. We used fluorescent two-dimensional differential gel electrophoresis to investigate the expression profile. We found 16 differentially expressed proteins in the fronto-parietal cortex and 35 proteins in the thalamus. It is known that SWD genesis correlates with the transitional state of sleep–wake cycle thus we performed meta-analysis of the altered proteins in relation to inflammation, epilepsy as well as sleep. The analysis revealed that all categories are highly represented by the altered proteins and these protein-sets have considerable overlap. Protein network modeling suggested that the alterations in the proteome were largely induced by the immune response, which invokes the NFkB signaling pathway.

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Why is it important?

The proteomics and computational analysis verified the known functional interplay between inflammation, epilepsy and sleep and highlighted proteins that are involved in their common synaptic mechanisms. Our physiological findings support the phenomenon that high dose of peripheral LPS injection increases SWD-number, modifies its duration as well as the sleep–wake stages and decreases body temperature.

Perspectives

The peripheral inflammatory response could induce remodeling of the brain proteome, and this remodeling could directly involve several proteins of the synaptic region. We suggest here three data-driven hypotheses for further studies on the influence of peripherally induced inflammation on brain functions. Our data suggest a complex and sustained change in the signaling system, mitochondrial metabolism and synaptic transmission after peripheral application of LPS that could be mainly driven by the immune reaction triggered elevation of cytokine levels in the brain.

Dr Zsolt Kovacs
Eötvös Loránd University

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This page is a summary of: Brain protein expression changes in WAG/Rij rats, a genetic rat model of absence epilepsy after peripheral lipopolysaccharide treatment, Brain Behavior and Immunity, January 2014, Elsevier,
DOI: 10.1016/j.bbi.2013.09.001.
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