Abstract
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.
Highlights
Prion diseases are fatal neurodegenerative diseases linked to the transformation of normal prion protein (PrPC) into an abnormal prion protein (PrPRes) which is transmitted from one cell to another causing neuron loss, astrocytic gliosis, microglia activation, and, frequently, spongiform change
Two-way analysis of variance (ANOVA) revealed a significant interaction between sCJD MM1-inoculation and the progression of the incubation time for aqp4 [F [2,16] = 6.960 (P = 0.0058)], mpc1 [F [2,16] = 5.302 (P = 0.0154)], and mct4 [F [2,15] = 5.066 (P = 0.02)] gene expression (Figure 1a)
Two-way ANOVA revealed a significant effect of sCJD MM1-inoculation for gfap [F [1,16] = 17.49 (P = 0.0006)] and slc1a2 [F [1,16] = 9.008 (P = 0.0077)] gene expression
Summary
Prion diseases are fatal neurodegenerative diseases linked to the transformation of normal prion protein (PrPC) into an abnormal prion protein (PrPRes) which is transmitted from one cell to another causing neuron loss, astrocytic gliosis, microglia activation, and, frequently, spongiform change. This transformation leads to devastating effects on the central nervous system including abnormal behaviour in animals, and cognitive impairment and rapid dementia in humans. The present study was designed to assess the involvement of oligo dendrocytes and astrocytes at preclinical and clinical stages in tg340 mice inoculated with human brain homogenates of sCJD. The study was aimed at gaining information about oligodendrocyte and astrocyte vul nerability at preclinical stages and with disease progres sion in a validated model of experimental CJD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
