Liu Xi-Lin, Feng Xiao-Li, Wang Guang-Ming, Gong Bin-Bin, Ahmad Waqas, Liu Nan-Nan, Zhang Yuan-Yuan, Yang Li, Ren Hong-Lin, Cui Shu-Sen
China-Japan Union Hospital of Jilin University, Key Laboratory of Zoonosis Research, Ministry of Education/Institute of Zoonosis, Jilin University, Changchun 130062, China.
Biological safety protection third-level laboratory, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
J Vet Res. 2017 Apr 4;61(1):11-22. doi: 10.1515/jvetres-2017-0002. eCollection 2017 Mar.
The functions and mechanisms of prion proteins (PrP) are currently unknown, but most experts believe that deformed or pathogenic prion proteins (PrP) originate from PrP, and that there may be plural main sites for the conversion of normal PrP into PrP. In order to better understand the mechanism of PrP transformation to PrP, the most important step is to determine the replacement or substitution site.
BALB/c mice were challenged with prion RML strain and from 90 days post-challenge (dpc) mice were sacrificed weekly until all of them had been at 160 dpc. The ultra-structure and pathological changes of the brain of experimental mice were observed and recorded by transmission electron microscopy.
There were a large number of pathogen-like particles aggregated in the myelin sheath of the brain nerves, followed by delamination, hyperplasia, swelling, disintegration, phagocytic vacuolation, and other pathological lesions in the myelin sheath. The aggregated particles did not overflow from the myelin in unstained samples. The phenomenon of particle aggregation persisted all through the disease course, and was the earliest observed pathological change.
It was deduced that the myelin sheath and lipid rafts in brain nerves, including axons and dendrites, were the main sites for the conversion of PrP to PrP, and the PrP should be formed directly by the conversion of protein conformation without the involvement of nucleic acids.
朊病毒蛋白（PrP）的功能和机制目前尚不清楚，但大多数专家认为，变形或致病的朊病毒蛋白（PrP）起源于PrP，并且正常PrP转化为PrP可能存在多个主要位点。为了更好地理解PrP转化为PrP的机制，最重要的一步是确定替换或取代位点。
用朊病毒RML株攻击BALB/c小鼠，在攻击后90天（dpc）开始，每周处死小鼠，直至所有小鼠都达到160 dpc。通过透射电子显微镜观察并记录实验小鼠大脑的超微结构和病理变化。
在脑神经髓鞘中有大量病原体样颗粒聚集，随后髓鞘出现分层、增生、肿胀、崩解、吞噬空泡化等病理病变。在未染色的样本中，聚集颗粒未从髓鞘中溢出。颗粒聚集现象在整个病程中持续存在，是最早观察到的病理变化。
推断脑神经中的髓鞘和脂筏，包括轴突和树突，是PrP转化为PrP的主要位点，并且PrP应该是由蛋白质构象直接转化形成的，无需核酸参与。
