Related Experiment Video
Updated: Oct 29, 2025
Dissection and Isolation of Murine Glia from Multiple Central Nervous System Regions
Published on: June 4, 2020
Differential astrocyte and oligodendrocyte vulnerability in murine Creutzfeldt-Jakob disease
Pol Andrés-Benito1, Margarita Carmona1, Jean Yves Douet2
1Department of Pathology and Experimental Therapeutics, University of Barcelona; Biomedical Research Centre of Neurodegenerative Diseases (CIBERNED), Institute of Health Carlos III, Ministry of Economy, Innovation and Competitiveness, Hospitalet De Llobregat; Bellvitge Institute of Biomedical Research (IDIBELL); Institute of Neurosciences, University of Barcelona, Barcelona; Spain.
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.
Insights
This study reveals that astrocytes react early in prion disease, while oligodendrocytes and myelin are damaged later. These findings highlight oligodendrocyte vulnerability in Creutzfeldt-Jakob disease pathogenesis.
Area of Science:
- Neuroscience
- Prion Biology
- Cellular Pathology
Background:
- Creutzfeldt-Jakob disease (CJD) is a fatal prion disease.
- Understanding glial cell responses is crucial for CJD pathogenesis research.
Purpose of the Study:
- To investigate glial cell vulnerability and reactivity in a mouse model of human CJD.
- To assess astrocyte and oligodendrocyte responses at different disease stages.
Main Methods:
- Utilized the tg340 transgenic mouse model expressing human PrP.
- Analyzed gene and protein expression of glial markers (GFAP, AQP4, Olig2, MBP) at various time points post-inoculation.
- Quantified astrocyte, microglia, and oligodendrocyte numbers in the striatum.
Main Results:
- Astrocyte markers (GFAP, AQP4) increased early (120-180 days post-inoculation, dpi).
- Oligodendrocyte and myelin markers (Olig1, Olig2, MBP) were initially preserved but showed vulnerability later (180 dpi).
- Increased astrocytes and microglia, with reduced oligodendrocytes and MBP, were observed at advanced stages (180 dpi).
Conclusions:
- Astrocytes exhibit early reactive responses in murine CJD.
- Oligodendrocytes and myelin are vulnerable at advanced stages of the disease.
- These findings confirm oligodendrocyte involvement in CJD pathogenesis.
