Prion protein complexed to a DNA aptamer induce behavioral and synapse dysfunction in mice.

Area of Science:

• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases caused by prion protein (PrP) conversion.
• In vitro studies show nucleic acids can induce PrP aggregation, but in vivo effects remain largely unexplored.

Purpose of the Study:

• To investigate the in vivo effects of PrP aggregates formed with the D67 DNA aptamer.
• To establish a mouse model for studying prion-induced neurotoxicity and cognitive dysfunction.

Main Methods:

• Recombinant PrP (rPrP) was aggregated with the D67 aptamer.
• Aggregates were injected into the lateral ventricle of Swiss mice.
• Behavioral, cognitive, and histological analyses were performed.

Main Results:

• rPrP:D67 aggregates did not affect emotional or motor behavior.
• Mice developed cognitive impairment and hippocampal synapse loss.
• Intense glial cell activation was observed in the hippocampus.

Conclusions:

• In vivo administration of rPrP:D67 aggregates provides a model for studying PrP neurotoxicity.
• Glial cell activation is implicated in the cognitive deficits associated with prion diseases.