| First Author | Ratté S | Year | 2008 |
| Journal | Neurobiol Dis | Volume | 32 |
| Issue | 1 | Pages | 96-104 |
| PubMed ID | 18638557 | Mgi Jnum | J:140361 |
| Mgi Id | MGI:3813415 | Doi | 10.1016/j.nbd.2008.06.007 |
| Citation | Ratte S, et al. (2008) Hippocampal bursts caused by changes in NMDA receptor-dependent excitation in a mouse model of variant CJD. Neurobiol Dis 32(1):96-104 |
| abstractText | Prion diseases are heterogeneous in clinical presentation, suggesting that different prion diseases have distinct pathophysiological changes. To understand the pathophysiology specific to variant Creutzfeldt-Jakob Disease (vCJD), in vitro electrophysiological studies were performed in a mouse model in which human-derived vCJD prions were transmitted to transgenic mice expressing human instead of murine prion protein. Paired-pulse stimulation of the Schaffer collaterals evoked hypersynchronous bursting in the hippocampus of vCJD-inoculated mice; comparable bursts were never observed in control or Prnp knockout mice, or in mice inoculated with a strain of prion associated with classical CJD. Furthermore, NMDA receptor-mediated excitation was increased in vCJD-inoculated mice. Using pharmacological experiments and computer simulations, we demonstrate that the increase in NMDA receptor-mediated excitation is necessary and sufficient to explain the distinctive bursting pattern in vCJD. These pathophysiological changes appear to result from a prion strain-specific gain-of-function and may explain some of the distinguishing clinical features of vCJD. |
