Changes of tau profiles in brains of the hamsters infected with scrapie strains 263 K or 139 A possibly associated with the alteration of phosphate kinases.
BACKGROUND
Phospho-tau deposition has been described in a rare genetic human prion disease, Gerstmann-Sträussler-Scheinker syndrome, but is not common neuropathological picture for other human and animal transmissible spongiform encephalopathies (TSEs). This study investigated the possible changes of tau and phosphorylated tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in scrapie experimental animals.


METHODS
The profiles of tau and p-tau (p-tau, at Ser396, Ser404, and Ser202/Thr205) in the brain tissues of agents 263K- or 139A-infected hamsters were evaluated by Western blots and real-time PCR. Meanwhile, the transcriptional and expressive levels of GSK3beta and CDK5 in the brains were tested.


RESULTS
The contents of total tau and p-tau at Ser202/Thr205 increased, but p-tau at Ser396 and Ser404 decreased at the terminal stages, regardless of scrapie strains. Transcriptional levels of two tau isoforms were also increased. Additionally, it showed higher CDK5, but lower GSK3beta transcriptional and expressive levels in the brains of scrapie-infected animals. Analysis of brain samples collected from different times after inoculated with agent 263 K revealed that the changes of tau profiles and phosphate kinases were time-relative events.


CONCLUSIONS
These data suggest that changes of profiles of p-tau at Ser396, Ser404 and Ser202/Thr205 are illness-correlative phenomena in TSEs, which may arise of the alteration of phosphate kinases. Alteration of tau, p-tau (Ser396, Ser404, and Ser202/Thr205), GSK3beta and CDK5 were either intermediate or consequent events in TSE pathogenesis and proposed the potential linkage of these bioactive proteins with the pathogenesis of prion diseases.
Wang
Gui-Rong
GR
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing 100052, PR China.
Shi
Song
S
Gao
Chen
C
Zhang
Bao-Yun
BY
Tian
Chan
C
Dong
Chen-Fang
CF
Zhou
Rui-Min
RM
Li
Xiao-Li
XL
Chen
Cao
C
Han
Jun
J
Dong
Xiao-Ping
XP
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000473:pathology*; D006224:Cricetinae; D051360:Cyclin-Dependent Kinase 5 / Q000096:biosynthesis; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta; D008647:Mesocricetus; D010710:Phosphates / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011494:Protein Kinases / Q000378:metabolism*; D012608:Scrapie / Q000473:pathology*; D016875:tau Proteins / Q000378:metabolism*
D010710:Phosphates; D016875:tau Proteins; D011494:Protein Kinases; D051360:Cyclin-Dependent Kinase 5; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3