Department of Pathology and Infectious Diseases, Royal Veterinary College, North Mymms, Herts, AL9 7TA, UK.
Neurotox Res. 2010 Apr;17(3):203-14. doi: 10.1007/s12640-009-9093-2. Epub 2009 Jul 31.
A loss of synapses is characteristic of the early stages of the prion diseases. Here we modelled the synapse damage that occurs in prion diseases by measuring the amount of synaptophysin, a pre-synaptic membrane protein essential for neurotransmission, in cortical or hippocampal neurones incubated with the disease associated isoform of the prion protein (PrP(Sc)), or with the prion-derived peptide PrP82-146. The addition of PrP(Sc) or PrP82-146 caused a dose-dependent reduction in the synaptophysin content of PrP wildtype neurones indicative of synapse damage. They did not affect the synaptophysin content of PrP null neurones. The loss of synaptophysin in PrP wildtype neurones was preceded by the accumulation of PrP82-146 within synapses. Since supplements containing polyunsaturated fatty acids (PUFA) are frequently taken for their perceived health benefits including reported amelioration of neurodegenerative conditions, the effects of some common PUFA on prion-mediated synapse damage were examined. Pre-treatment of cortical or hippocampal neurones with docosahexaenoic (DHA) or eicosapentaenoic acids (EPA) protected neurones against the loss of synaptophysin induced by PrP82-146 or PrP(Sc). This effect of DHA and EPA was selective as they did not alter the loss of synaptophysin induced by a snakevenom neurotoxin. The effects of DHA and EPA were associated with a significant reduction in the amount of FITC-PrP82-146 that accumulated within synapses. Such observations raise the possibility that supplements containing PUFA may protect against the synapse damage and cognitive loss seen during the early stages of prion diseases.
神经突触的丢失是朊病毒疾病早期的特征。在这里，我们通过测量皮质或海马神经元中突触小泡蛋白（一种对神经递质传递至关重要的前突触膜蛋白）的含量，来模拟朊病毒疾病中发生的突触损伤。将与疾病相关的朊病毒蛋白（PrP（Sc））或朊病毒衍生肽 PrP82-146 与皮质或海马神经元孵育。PrP（Sc）或 PrP82-146 的添加导致突触小泡蛋白含量在 PrP 野生型神经元中呈剂量依赖性降低，表明突触损伤。它们不影响 PrP 缺失神经元的突触小泡蛋白含量。PrP82-146 在突触内的积累先于 PrP 野生型神经元中突触小泡蛋白的丢失。由于含有多不饱和脂肪酸（PUFA）的补充剂经常因其被认为的健康益处而被服用，包括据报道对神经退行性疾病的改善，因此研究了一些常见的 PUFA 对朊病毒介导的突触损伤的影响。用二十二碳六烯酸（DHA）或二十碳五烯酸（EPA）预处理皮质或海马神经元可防止 PrP82-146 或 PrP（Sc）诱导的突触小泡蛋白丢失。DHA 和 EPA 的这种作用是选择性的，因为它们不会改变蛇神经毒素诱导的突触小泡蛋白丢失。DHA 和 EPA 的作用与 FITC-PrP82-146 在突触内积累量的显著减少有关。这些观察结果提出了这样一种可能性，即含有 PUFA 的补充剂可能有助于预防朊病毒疾病早期阶段出现的突触损伤和认知丧失。
