title: Cerebral adenosine A₁ receptors are upregulated in rodent encephalitis.
abstract: Adenosine A1 receptors (A1Rs) are implied in the modulation of neuroinflammation. Activation of cerebral A1Rs 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 A1Rs. Two groups of animals were studied: Infected rats (n=7) were intranasally inoculated with herpes simplex virus-1 (HSV-1, 1 × 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-(11)C-methyl-3-propyl-xanthine ((11)C-MPDX). Tracer clearance from plasma and partition coefficient (K₁/k₂ 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 virus infected rats. Tracer binding potential (k₃/k₄ 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.
authors: University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ Groningen, The Netherlands.
authors: Soumen
authors: S
authors: Paul
authors: University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ Groningen, The Netherlands.
authors: Shivashankar
authors: S
authors: Khanapur
authors: University of Groningen, University Medical Center Groningen, Department of Medical Oncology, Hanzeplein 1, 9713GZ Groningen, The Netherlands.
authors: Wytske
authors: W
authors: Boersma
authors: University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ Groningen, The Netherlands.
authors: Jurgen W
authors: JW
authors: Sijbesma
authors: Tokyo Metropolitan Institute of Gerontology, Research Team for Neuroimaging, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, JAPAN.
authors: Kiichi
authors: K
authors: Ishiwata
authors: University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ Groningen, The Netherlands.
authors: Philip H
authors: PH
authors: Elsinga
authors: University of Groningen, Center for Behaviour and Neurosciences, Nijenborgh 7, 9747AG Groningen, The Netherlands.
authors: Peter
authors: P
authors: Meerlo
authors: University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ Groningen, The Netherlands.
authors: Janine
authors: J
authors: Doorduin
authors: University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ Groningen, The Netherlands.
authors: Rudi A
authors: RA
authors: Dierckx
authors: University of Groningen, University Medical Center Groningen, Nuclear Medicine and Molecular Imaging, Hanzeplein 1, 9713GZ Groningen, The Netherlands. Electronic address: a.van.waarde@umcg.nl.
authors: Aren
authors: A
authors: van Waarde
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001921:Brain / Q000378:metabolism*; D018792:Encephalitis, Viral / Q000000981:diagnostic imaging / Q000378:metabolism*; D015658:HIV Infections / Q000000981:diagnostic imaging / Q000378:metabolism*; D007155:Immunologic Factors / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D049268:Positron-Emission Tomography / Q000379:methods / Q000662:veterinary*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014018:Tissue Distribution; D015854:Up-Regulation; D014970:Xanthines / Q000493:pharmacokinetics*
chemical_list: C451639:1-methyl-8-dicyclopropylmethyl-1-methyl-3-propylxanthine; D007155:Immunologic Factors; D019275:Radiopharmaceuticals; D043682:Receptor, Adenosine A1; D014970:Xanthines
keywords: Adenosine A1 receptors; Herpes simplex virus-1; Kinetic modeling; MicroPET; Neuroinflammation; Rats