A Neuronal Culture System to Detect Prion Synaptotoxicity

PLoS Pathogens

Maria Carmen Garza¹  Holger Wille¹  David A. Harris²  Thibaut Imberdis²  Cheng Fang² 

[1] Department of Biochemistry and Centre for Prions and Protein Folding Diseases, University of Alberta, Edmonton, Alberta, Canada;Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts, United States of America

关键词: Neuronal dendrites;    Neurons;    Prion diseases;    Animal prion diseases;    Silver staining;    Proteases;    Neuronal death;    Neuronal morphology;   

DOI  :  10.1371/journal.ppat.1005623

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Synaptic pathology is an early feature of prion as well as other neurodegenerative diseases. Although the self-templating process by which prions propagate is well established, the mechanisms by which prions cause synaptotoxicity are poorly understood, due largely to the absence of experimentally tractable cell culture models. Here, we report that exposure of cultured hippocampal neurons to PrPSc, the infectious isoform of the prion protein, results in rapid retraction of dendritic spines. This effect is entirely dependent on expression of the cellular prion protein, PrPC, by target neurons, and on the presence of a nine-amino acid, polybasic region at the N-terminus of the PrPC molecule. Both protease-resistant and protease-sensitive forms of PrPSc cause dendritic loss. This system provides new insights into the mechanisms responsible for prion neurotoxicity, and it provides a platform for characterizing different pathogenic forms of PrPSc and testing potential therapeutic agents.

【 授权许可】

CC BY