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Cerebral adenosine A1 receptors are upregulated in rodent encephalitis

Paul, S., Khanapur, S., Boersma, W., Sijbesma, J. W., Ishiwata, K., Elsinga, P. H., Meerlo, P., Doorduin, J., Dierckx, R. A. & van Waarde, A., 2014, In : Neuroimage. 92, p. 83-89

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DOI

Adenosine A(1) receptors (A(1) Rs) are implied in the modulation of neuroinflammation. Activation of cerebral A(1) Rs acts as a brake on the microglial response after traumatic brain injury and has neuroprotective properties in animal models of Parkinson's disease and multiple sclerosis. Neuroinflammatory processes in turn may affect the expression of A1Rs, but the available data is limited and inconsistent. Here, we applied an animal model of encephalitis to assess how neuroinflammation affects the expression of A1 Rs. Two groups of animals were studied: Infected rats (n=7) were intranasally inoculated with herpes simplex virus-1 (HSV-1, 1 x 10(7) plaque forming units), sham-infected rats (n=6) received only phosphate-buffered saline. Six or seven days later, microPET scans (60 min with arterial blood sampling) were made using the tracer 8-dicyclopropyl-1-C-11-methy1-3-propyl-xanthine (C-11-MPDX). Tracer clearance from plasma and partition coefficient (K-1/k(2) estimated from a 2-tissue compartment model fit) were not significantly altered after virus infection. PET tracer distribution volume calculated from a Logan plot was significantly increased in the hippocampus (+37%) and medulla (+27%) of virug infected rats. Tracer binding potential (k(3)/k(4) estimated from the model fit) was significantly increased in the cerebellum (+87%) and the medulla (+148%) which may indicate increased A1R expression. This was confirmed by immunohistochemical analysis showing a strong increase of A1R immunoreactivity in the cerebellum of HSV-1-infected rats. Both the quantitative PET data and immunohistochemical analysis indicate that A1Rs are upregulated in brain areas where active virus is present. (C) 2014 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)83-89
JournalNeuroimage
Volume92
Publication statusPublished - 2014

    Keywords

  • encephalitis, herpes simplex virus-1, neuroinflammation, brain, adenosine, adenosine A1 receptors, positron emission tomography, PET, MicroPET

ID: 15815142