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Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression

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Abstract

We have previously shown that peripherally restricted acute phase response (APR) elicited by intraperitoneal (i.p.) injection of a viral mimic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to excitotoxic insult as seen from profoundly exacerbated kainic acid (KA)-induced seizures. In the present study, we found that this hypersusceptibility was protracted for up to 72 h. RT-PCR profiling of hippocampal gene expression revealed rapid upregulation of 23 genes encoding cytokines, chemokines and chemokine receptors generally within 6 h after PIC challenge. The expression of most of these genes decreased by 24 h. However, two chemokine genes, i.e., Ccl19 and Cxcl13 genes, as well as two chemokine receptor genes, Ccr1 and Ccr7, remained upregulated for 72 h suggesting their possible involvement in the induction and sustenance of seizure hypersusceptibility. Also, 12 genes encoding proteins related to glutamatergic and GABAergic neurotransmission featured initial upregulation or downregulation followed by gradual normalization. The upregulation of the Gabrr3 gene remained upregulated at 72 h, congruent with its plausible role in the hypersusceptible phenotype. Moreover, the expression of ten microRNAs (miRs) was rapidly affected by PIC challenge, but their levels generally exhibited oscillating profiles over the time course of seizure hypersusceptibility. These results indicate that protracted seizure susceptibility following peripheral APR is associated with a robust polygenic response in the hippocampus.

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Acknowledgments

This study was partly supported by a Research Funding Development Grant from WVU School of Medicine, and by the National Institutes of Health/National Institute of General Medical Sciences, U54GM104942. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The authors express their gratitude to Dr. Matsumoto for the use of the PAS-Open field automated monitoring system. The authors also would like to thank Mr. Brent Lally for proofreading this manuscript.

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  1. Department of Neurobiology and Anatomy, West Virginia University School of Medicine, 1 Medical Center Dr., 4052 HSCN, P.O. Box 9128, Morgantown, WV, 26506-9128, USA

    Lindsay T. Michalovicz & Gregory W. Konat

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Correspondence to Gregory W. Konat.

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Michalovicz, L.T., Konat, G.W. Peripherally restricted acute phase response to a viral mimic alters hippocampal gene expression. Metab Brain Dis 29, 75–86 (2014). https://doi.org/10.1007/s11011-013-9471-6

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