Neuroimmune Response in Natural Preclinical Scrapie after Dexamethasone Treatment.

Isabel M Guijarro,Juan J Badiola,Moisés Garcés,Belén Marín,Marta Monzón,Tomás Barrio,Alicia Otero

doi:10.3390/ijms21165779

Isabel M Guijarro, Juan J Badiola + Show 5 more

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https://doi.org/10.3390/ijms21165779

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Abstract

A recently published report on chronic dexamethasone treatment for natural scrapie supported the hypothesis of the potential failure of astroglia in the advanced stage of disease. Herein, we aimed to extend the aforementioned study on the effect of this anti-inflammatory therapy to the initial phase of scrapie, with the aim of elucidating the natural neuroinflammatory process occurring in this neurodegenerative disorder. The administration of this glucocorticoid resulted in an outstanding reduction in vacuolation and aberrant protein deposition (nearly null), and an increase in glial activation. Furthermore, evident suppression of IL-1R and IL-6 and the exacerbation of IL-1α, IL-2R, IL-10R and IFNγR were also demonstrated. Consequently, the early stage of the disease is characterized by an intact neuroglial response similar to that of healthy individuals attempting to re-establish homeostasis. A complex network of neuroinflammatory markers is involved from the very early stages of this prion disease, which probably becomes impaired in the more advanced stages. The in vivo animal model used herein provides essential observations on the pathogenesis of natural scrapie, as well as the possibility of establishing neuroglia as potential target cells for anti-inflammatory therapy.

Highlights

Scrapie is the prototype of prion diseases, and is one of the most common neurological diseases in sheep, together with coenurosis and leptospirosis, among others [1].Several reasons prompted us to perform this study on the neuroinflammatory response of naturally affected animals in the preclinical stage of scrapie
A recently published report on chronic dexamethasone treatment for natural scrapie supported the hypothesis of the potential failure of astroglia in the advanced stage of disease
CytoIkninreelaDtioentetcotitohne neuroinflammatory markers assessed here, our immunohistochemical results revealed that preclinical sheep showed a very significant increase in IL-1 expression in the frontal cortex (Fc) when

Summary

Introduction

Scrapie is the prototype of prion diseases, and is one of the most common neurological diseases in sheep, together with coenurosis and leptospirosis, among others [1].Several reasons prompted us to perform this study on the neuroinflammatory response of naturally affected animals in the preclinical stage of scrapie. Neuroinflammation is an intrinsic concept in the neurodegenerative process [2,3], in the context of which cytokines have gained huge attention because they have been demonstrated to be involved in the inflammatory processes leading to neurodegeneration [3,4,5] This complex immune reaction is carried out by neuroglia in this and other neurodegenerative processes. Whether it really plays a neurotoxic [6,7,8,9] or neuroprotective [10,11] role is still unknown This host response has been demonstrated to be involved in the neurodegeneration of prion diseases in sheep [12,13,14], coinciding with the onset of clinical signs in the murine model [15] and in Creutzfeldt Jakob disease (CJD) [6]. Cytokines have been proven to be relevant mediators in cellular communication in several models of this group of diseases [6,7,8,12,15,16,17]

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