Salès N, Rodolfo K, Hässig R, Faucheux B, Di Giamberardino L, Moya K L
INSERM U.334, Service Hospitalier Frédéric Joliot, CEA, Orsay, France.
Eur J Neurosci. 1998 Jul;10(7):2464-71. doi: 10.1046/j.1460-9568.1998.00258.x.
The presence of an abnormal, protease-resistant form of the prion protein (PrP) is the hallmark of various forms of transmissible spongiform encephalopathies (TSE) which can affect a number of mammalian species, including humans. The normal, cellular form of this protein, PrPc, while abundant in brain is also present in many tissues and a number of species. In order to address the unresolved question of the precise localization of normal cerebral PrPc, we used a free-floating immunohistochemistry procedure to localize the protein at both the light and the electron microscopic levels in the brain of three TSE-sensitive species: hamster, macaque and humans. This method shows that PrPc is abundant in synaptic terminal fields in olfactory bulb, limbic-associated structures and in the striato-nigral complex, whereas many other regions of the hamster brain are essentially devoid of immunoreactivity. With the striking exception of the olfactory nerve, in which axons are continually growing throughout life, PrPc is not abundant in fibre pathways. PrPc distribution in the primate hippocampus and cortex is very similar to the distribution observed in hamster. PrPc was present at synaptic profiles as shown by immunoelectron microscopy, but was not detectable in neuronal perikaryon either by light or electron microscopy. Our results show that PrPc is abundant in a number of brain structures known for ongoing plasticity, and are consistent with the hypothesis that the protein also plays a role in synaptic function.
异常的、抗蛋白酶的朊病毒蛋白（PrP）的存在是各种形式的传染性海绵状脑病（TSE）的标志，这些疾病可影响包括人类在内的许多哺乳动物物种。这种蛋白质的正常细胞形式PrPc，虽然在大脑中含量丰富，但也存在于许多组织和多个物种中。为了解决正常脑PrPc精确定位这一尚未解决的问题，我们采用了一种游离免疫组织化学方法，在光镜和电镜水平上对三种对TSE敏感的物种（仓鼠、猕猴和人类）大脑中的该蛋白质进行定位。该方法显示，PrPc在嗅球、边缘相关结构和黑质纹状体复合体的突触终末区域含量丰富，而仓鼠大脑的许多其他区域基本没有免疫反应性。除了嗅神经这一显著例外（其轴突在整个生命过程中持续生长），PrPc在纤维通路中含量不丰富。PrPc在灵长类动物海马体和皮质中的分布与在仓鼠中观察到的分布非常相似。免疫电镜显示PrPc存在于突触结构中，但在光镜或电镜下均未在神经元胞体中检测到。我们的结果表明，PrPc在许多以持续可塑性而闻名的脑结构中含量丰富，这与该蛋白质也在突触功能中发挥作用的假设一致。
