Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response.

Nara Lins,João Bento-Torres,Aline Passos,José Augusto Farias,Marcia Consentino Kronka Sosthenes,Pedro Fernando Da Costa Vasconcelos,Cristovam Wanderley Picanço-Diniz,Nonata Trévia,Jarila Assunção,Amanda Quintairos,José Antonio Picanço Diniz,Luiz Mourão

doi:10.1155/2016/3974648

Nara Lins, João Bento-Torres + Show 10 more

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https://doi.org/10.1155/2016/3974648

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Abstract

We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits.

Highlights

Infections and chronic neurodegenerative diseases acting together represent an increasing proportion in the health care budgets worldwide [1]
In contrast with virus infection transitory symptoms, chronic neurodegeneration of prion disease inflicts permanent symptoms that aggravate as disease progresses
We tested the hypothesis that an arbovirus infection would exacerbate the inflammatory response in a chronic neurodegeneration model of prion disease

Summary

Introduction

Infections and chronic neurodegenerative diseases acting together represent an increasing proportion in the health care budgets worldwide [1]. The Vesiculovirus Piry infection generates human disease characterized by rapid onset, high fever, headache, chills, photophobia, myalgia, dizziness, and weakness [11] and, in adult mice, a nonlethal CNS infection and injury to the limbic system including the hippocampus [12], a target region of the degenerative process induced by prion disease in mice [13]. This particularity to infect humans and damage the hippocampus of adult mice makes

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