Jefferys J G, Empson R M, Whittington M A, Prusiner S B
Department of Physiology and Biophysics, St Mary's Hospital Medical School, Imperial College, Norfolk Place, London, W2 1PG, UK.
Neurobiol Dis. 1994 Nov;1(1-2):25-30. doi: 10.1006/nbdi.1994.0004.
The human prion encephalopathy Creutzfeldt-Jakob disease often is manifest as rapidly progressing dementia with myoclonus and synchronous, periodic discharges. To investigate the electrophysiology of prion disease we used intra- and extra-cellular recordings from brain slices from Tg(SHaPrP+/+) 81 mice, which express Syrian hamster prion protein and which are susceptible to hamster-passaged scrapie isolates. Forty days after intracerebral inoculation with scrapie isolate Sc237, we recorded prolonged, epileptiform discharges in cortex and hippocampus. Neurological signs were subtle and histopathology was minimal. Central nervous system (CNS) dysfunction progressed; by 57 days the mice were ataxic, had spongiform histopathology and they died in <63 days. During the terminal phase, intrinsic neuronal properties changed dramatically and action potentials broadened from <4 to 20-100 ms in 30% of cortical cells. We conclude that brain dysfunction in experimental scrapie precedes clinical signs and spongiform histopathology, and is preserved in slices maintained in vitro, making it accessible to electrophysiological analysis.
人类朊病毒脑病克雅氏病通常表现为伴有肌阵挛和同步性、周期性放电的快速进展性痴呆。为了研究朊病毒病的电生理学，我们使用了来自Tg(SHaPrP+/+) 81小鼠脑片的细胞内和细胞外记录，这些小鼠表达叙利亚仓鼠朊病毒蛋白，并且对仓鼠传代的羊瘙痒病分离株易感。在用羊瘙痒病分离株Sc237进行脑内接种40天后，我们在皮层和海马中记录到了延长的癫痫样放电。神经学症状不明显，组织病理学变化轻微。中枢神经系统（CNS）功能障碍逐渐进展；到57天时，小鼠出现共济失调，具有海绵状组织病理学特征，并在63天内死亡。在终末期，神经元的内在特性发生了显著变化，30%的皮层细胞的动作电位从小于4毫秒加宽到20 - 100毫秒。我们得出结论，实验性羊瘙痒病中的脑功能障碍先于临床症状和海绵状组织病理学变化，并且在体外培养的脑片中得以保留，从而便于进行电生理学分析。
