Assessment of Glial Activation Response in the Progress of Natural Scrapie after Chronic Dexamethasone Treatment.

Isabel M Guijarro,Tomás Barrio,Belén Marín,Pol Andrés-Benito,Alicia Otero,Marta Monzón,Juan J Badiola,Isidro Ferrer,Moisés Garcés,Margarita Carmona

doi:10.3390/ijms21093231

Abstract

Neuroinflammation has been correlated with the progress of neurodegeneration in many neuropathologies. Although glial cells have traditionally been considered to be protective, the concept of them as neurotoxic cells has recently emerged. Thus, a major unsolved question is the exact role of astroglia and microglia in neurodegenerative disorders. On the other hand, it is well known that glucocorticoids are the first choice to regulate inflammation and, consequently, neuroglial inflammatory activity. The objective of this study was to determine how chronic dexamethasone treatment influences the host immune response and to characterize the beneficial or detrimental role of glial cells. To date, this has not been examined using a natural neurodegenerative model of scrapie. With this aim, immunohistochemical expression of glial markers, prion protein accumulation, histopathological lesions and clinical evolution were compared with those in a control group. The results demonstrated how the complex interaction between glial populations failed to compensate for brain damage in natural conditions, emphasizing the need for using natural models. Additionally, the data showed that modulation of neuroinflammation by anti-inflammatory drugs might become a research focus as a potential therapeutic target for prion diseases, similar to that considered previously for other neurodegenerative disorders classified as prion-like diseases.

Highlights

Prion diseases are a group of fatal neurodegenerative diseases affecting animal and human species and are caused by the conversion of cellular prion protein (PrPc) into a pathological isoform called pathological prion protein (PrPsc)
The specific objective of this study was to assess the effect of the synthetic GC dexamethasone (DEX) on the spread of scrapie in a natural sheep model, paying special attention to the differential expression of astroglial and microglial markers as main components of the host immune response in the brain
Some studies argue that DEX has minimal access to the CNS [67,68,69], the present study clearly demonstrates the successful efficacy of DEX to cross the blood–brain barrier, as evidenced by the strong astroglial reaction in treated controls

Summary

Introduction

Prion diseases are a group of fatal neurodegenerative diseases affecting animal and human species and are caused by the conversion of cellular prion protein (PrPc) into a pathological isoform called pathological prion protein (PrPsc). Several lines of research have found that this group of diseases shares neuropathological features, extracellular deposit of insoluble plaques of an aberrant protein, astrocytosis and microglial activation [10,11,12] with other human neurodegenerative disorders. The mechanism of induction and spread of protein misfolding within this group of diseases have led to include them in prion-like disorders [13], such as Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s (HD) diseases. In line with this fact, some studies have proposed using prion diseases as acceptable models to better understand the pathogenesis of prion-like disorders [14,15]

Objectives

Methods

Results

Conclusion