| First Author | Shin HY | Year | 2014 |
| Journal | Front Aging Neurosci | Volume | 6 |
| Pages | 207 | PubMed ID | 25202268 |
| Mgi Jnum | J:288689 | Mgi Id | MGI:6433183 |
| Doi | 10.3389/fnagi.2014.00207 | Citation | Shin HY, et al. (2014) Deficiency of prion protein induces impaired autophagic flux in neurons. Front Aging Neurosci 6:207 |
| abstractText | Normal cellular prion protein (PrP(C)) is highly expressed in the central nervous system. The Zurich I Prnp-deficient mouse strain did not show an abnormal phenotype in initial studies, however, in later studies, deficits in exploratory behavior and short- and long-term memory have been revealed. In the present study, numerous autophagic vacuoles were found in neurons from Zurich I Prnp-deficient mice. The autophagic accumulation in the soma of cortical neurons in Zurich I Prnp-deficient mice was observed as early as 3 months of age, and in the hippocampal neurons at 6 months of age. Specifically, there is accumulation of electron dense pigments associated with autophagy in the neurons of Zurich I Prnp-deficient mice. Furthermore, autophagic accumulations were observed as early as 3 months of age in the CA3 region of hippocampal and cerebral cortical neuropils. The autophagic vacuoles increased with age in the hippocampus of Zurich I Prnp-deficient mice at a faster rate and to a greater extent than in normal C57BL/6J mice, whereas the cortex exhibited high levels that were maintained from 3 months old in Zurich I Prnp-deficient mice. The pigmented autophagic accumulation is due to the incompletely digested material from autophagic vacuoles. Furthermore, a deficiency in PrP(C) may disrupt the autophagic flux by inhibiting autophagosome-lysosomal fusion. Overall, our results provide insight into the protective role of PrP(C) in neurons, which may play a role in normal behavior and other brain functions. |
