Differential astrocyte and oligodendrocyte vulnerability in murine Creutzfeldt-Jakob disease

ABSTRACT

Glial vulnerability to prions is assessed in murine Creutzfeldt-Jakob disease (CJD) using the tg340 mouse line expressing four-fold human PrP M129 levels on a mouse PrP null background at different days following intracerebral inoculation of sCJD MM1 brain tissues homogenates. The mRNA expression of several astrocyte markers, including glial fibrillary acidic protein (gfap), aquaporin-4 (aqp4), solute carrier family 16, member 4 (mct4), mitochondrial pyruvate carrier 1 (mpc1) and solute carrier family 1, member 2 (glial high-affinity glutamate transporter, slc1a2) increases at 120 and 180 dpi. In contrast, the mRNA expression of oligodendrocyte and myelin markers oligodendrocyte transcription factor 1 (olig1), olig2, neural/glial antigen 2 (cspg), solute carrier family 16, member 1 (mct1), myelin basic protein (mbp), myelin oligodendrocyte glycoprotein (mog) and proteolipid protein 1 (plp1) is preserved. Yet, myelin regulatory factor (myrf) mRNA is increased at 180 dpi. In the striatum, a non-significant increase in the number of GFAP-positive astrocytes and Iba1-immunoreactive microglia occurs at 160 dpi; a significant increase in the number of astrocytes and microglia, and a significant reduction in the number of Olig2-immunoreactive oligodendrocytes occur at 180 dpi. A decrease of MBP, but not PLP1, immunoreactivity is also observed in the striatal fascicles. These observations confirm the vulnerability and the reactive responses of astrocytes, together with the microgliosis at middle stages of prion diseases. More importantly, these findings show oligodendrocyte vulnerability and myelin alterations at advanced stages of murine CJD. They confirm oligodendrocyte involvement in the pathogenesis of CJD.

KEYWORDS:

• Prionopathy
• creutzdfeldt-jakob
• astrocytes
• oligodendrocytes
• myelin

Acknowledgments

We wish to thank T. Yohannan for editorial assistance.

Author’s contribution

IF and OA designed the study. OA, JYD and HC prepared the series of inoculated mice, killed the animals at established post-inoculation times, and prepared the samples for biochemical and morphological studies. PAB and MC carried out the biochemical and morphological studies. IF analysed the results and wrote the first version of the manuscript. The paper was circulated, corrected, and approved by all the authors.

Disclosure Statement

No relevant data.

Additional information

Funding

This work was co-financed by ERDF under the program Interreg Poctefa: RedPrion 148/16;ERDF [148/16];