Astrocyte-to-neuron intercellular prion transfer is mediated by cell-cell contact

Area of Science:

• Neuroscience
• Cell Biology
• Infectious Diseases

Background:

• Prion diseases stem from misfolded prion proteins (PrPSc) that propagate through intercellular transfer.
• The mechanism of prion spread within the central nervous system, particularly involving non-neuronal cells, remains largely unknown.
• Astrocytes, crucial for brain homeostasis, are early sites of prion accumulation, suggesting a potential role in disease propagation.

Purpose of the Study:

• To investigate whether astrocytes are involved in the intercellular transfer of prions within the central nervous system.
• To determine the mechanism by which prion-infected astrocytes disseminate prions to neurons.

Main Methods:

• Co-culture systems were established using primary prion-infected astrocytes and either granule neurons or neuronal cell lines.
• The study analyzed prion transfer via astrocyte secretion and direct cell-to-cell contact, including tunneling nanotubes.

Main Results:

• Prion-infected astrocytes were shown to effectively disseminate prions to neurons in co-culture systems.
• While astrocytes secrete PrP, this is an inefficient route for prion infectivity transfer.
• Efficient prion transfer from astrocytes to neurons necessitates direct cell contact, potentially via tunneling nanotubes containing PrPSc and endolysosomal vesicles.

Conclusions:

• Astrocytes play a significant role in intercellular prion transfer to neurons within the central nervous system.
• Direct cell contact, possibly through tunneling nanotubes, is the primary mechanism for efficient prion dissemination by astrocytes.
• The involvement of astrocytes in prion transfer suggests they may significantly influence the progression of prion diseases.