| First Author | Schmitz M | Year | 2014 |
| Journal | Mol Neurobiol | Volume | 50 |
| Issue | 3 | Pages | 923-36 |
| PubMed ID | 24604355 | Mgi Jnum | J:315536 |
| Mgi Id | MGI:6829176 | Doi | 10.1007/s12035-014-8655-3 |
| Citation | Schmitz M, et al. (2014) Loss of prion protein leads to age-dependent behavioral abnormalities and changes in cytoskeletal protein expression. Mol Neurobiol 50(3):923-36 |
| abstractText | The cellular prion protein (PrPC) is a highly conserved protein whose exact physiological role remains elusive. In the present study, we investigated age-dependent behavioral abnormalities in PrPC-knockout (Prnp0/0) mice and wild-type (WT) controls. Prnp0/0 mice showed age-dependent behavioral deficits in memory performance, associative learning, basal anxiety, and nest building behavior. Using a hypothesis-free quantitative proteomic investigation, we found that loss of PrPC affected the levels of neurofilament proteins in an age-dependent manner. In order to understand the biochemical basis of these observations, we analyzed the phosphorylation status of neurofilament heavy chain (NF-H). We found a reduction in NF-H phosphorylation in both Prnp0/0 mice and in PrPC-deficient cells. The expression of Fyn and phospho-Fyn, a potential regulator for NF phosphorylation, was associated with PrPC ablation. The number of beta-tubulin III-positive neurons in the hippocampus was diminished in Prnp0/0 mice relative to WT mice. These data indicate that PrPC plays an important role in cytoskeletal organization, brain function, and age-related neuroprotection. Our work represents the first direct biochemical link between these proteins and the observed behavioral phenotypes. |
