title: Deficiency of prion protein induces impaired autophagic flux in neurons.
abstract: Normal cellular prion protein (PrP(C)) is highly expressed in the central nervous system. The Zürich 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 Zürich I Prnp-deficient mice. The autophagic accumulation in the soma of cortical neurons in Zürich 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 Zürich 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 Zürich 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 Zürich 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.
authors.affiliation: Ilsong Institute of Life Science, Hallym University Anyang, Gyeonggi-do, South Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Shin
authors.affiliation: Ilsong Institute of Life Science, Hallym University Anyang, Gyeonggi-do, South Korea.
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY, USA.
authors.forename: Richard I
authors.initials: RI
authors.lastname: Carp
authors.affiliation: Ilsong Institute of Life Science, Hallym University Anyang, Gyeonggi-do, South Korea ; Department of Biomedical Gerontology, Graduate School of Hallym University Chuncheon, Gangwon-do, South Korea.
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Choi
authors.affiliation: Ilsong Institute of Life Science, Hallym University Anyang, Gyeonggi-do, South Korea ; Department of Microbiology, College of Medicine, Hallym University Chuncheon, Gangwon-do, South Korea.
authors.forename: Yong-Sun
authors.initials: YS
authors.lastname: Kim
keywords: Prnp-deficient mice; autophagic flux; autophagy; lipofuscin pigmented autophagy; prion protein