在一項小鼠研究中,，研究人員表示，如果及早發(fā)現(xiàn),，或許可以治愈朊病毒疾病,。研究作者認(rèn)為降低患者病人腦內(nèi)朊蛋白表現(xiàn)量，將是一種有效的早期治療方法,。同時,，此項研究還提出了一項檢驗朊病毒疾病治療效果的新方法：檢測朊病毒感染的小鼠的認(rèn)知能力。
在這篇新的研究中,，作者模仿人類的朊病毒疾病,，而構(gòu)建了發(fā)生認(rèn)知和行為損傷的小鼠模型?；疾〉男∈笤谠缙诰捅憩F(xiàn)出辨認(rèn)新物體,、挖掘的障礙。同時,，在腦細(xì)胞中的一些信號路徑也發(fā)生了損傷,。清除小鼠腦中的朊蛋白后，研究人員發(fā)現(xiàn)患病小鼠的上述癥狀都逐漸消失了,，并且恢復(fù)了正常,。
朊病毒感染的小鼠的研究顯示，神經(jīng)元的功能和存活是相當(dāng)重要的,，研究人員據(jù)此提出了一個治療方案,，就是直接針對神經(jīng)元中的朊蛋白。他們希望這種方法也適用于人類的朊病毒感染疾病之治療,。
本研究作者為Giovanna Mallucci,，該研究成果發(fā)表于2007年2月1日的Neuron中。
(資料來源 : Bio.com)
部分英文原文：
Object Memory Is Impaired Early in Prion Infection
Figure 1. The Ability to Discriminate Novel Objects Is Lost in Prion-Infected Mice but Recovers when Neuronal PrPC Is Depleted, in Parallel with Reversal of Pathological Change
(A) Mice are allowed to explore two objects in an arena during the learning phase of the test; then, after a retention interval, they are exposed to a novel object (test phase). Time spent actively exploring the novel object compared to the familiar one is a measure of object-recognition memory and is expressed as the ratio of exploratory preference. (B) Prion-infected tg37 (blue bars) and NFH-Cre/tg37 mice (red bars) showed normal object-recognition memory at 7 wpi, with preferential exploration of the novel object. This was significantly impaired in all mice by 8 wpi, but recovered in mice with Cre-mediated PrP depletion at 9 wpi. Recovery was sustained up to 30 wpi. (C) Hematoxylin and eosin-stained sections of hippocampi from prion-infected tg37 and NFH-Cre/tg37 mice have normal appearance at 6 wpi (panels [A] and [D]). Spongiosis develops in all animals (panels [B] and [E]) by 8 wpi when memory is impaired, but by 10 wpi this has reversed in mice with Cre-mediated depletion (panel [F]), in parallel with recovery of novel-object memory. (D) Reduced exploration of novel object is not due to prion-induced reduction in motor activity. Mice were tested for activity in the open field by measuring the number of squares crossed in an arena in 3 min. There was no decline in activity, but at 12 wpi tg37 mice were significantly more active than NFH-Cre/tg37 mice, consistent with previous findings in prion infection. n = 8–10 mice for all groups except at 8, 9, and 10 wpi when two groups of 8–10 mice each were tested. N = 7 at 12 wpi for tg37, and at 20–30 wpi for NFH-Cre/tg37 mice. Error bars represent standard error of the mean (SEM). Dashed line represents random exploration (exploratory preference = 1). p < 0.05; p < 0.01; p < 0.001 (Student's t test; two tails). Open arrow indicates onset of earliest signs of scrapie in tg37 mice (ss). Closed arrow indicates onset of Cre-mediated knockout. Scale bar represents 160 μm.
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PrP Depletion Reverses Early Cognitive Deficits
Loss of PrP expression due to Cre-mediated recombination in the hippocampi of NFH-Cre/tg37 mice after 8 wpi (or 9 weeks of age for uninfected mice) was confirmed by immunohistochemistry and RT-PCR for PrP mRNA expression at representative time points (Figure 2).
Figure 2. Cre-Mediated PrP Depletion Occurs after 8 wpi or 9 Weeks of Age in NFH-Cre/tg37 Mice
(A) Immunohistochemical detection of PrP using ICSM 35 antibody shows loss of PrP expression after 8 wpi (panels [b] and [c]). Box indicates CA1 region where neurophysiological recordings were made. (B) RT-PCR confirms reduction of PrP mRNA in hippocampal mRNA extracts from NFH-Cre/tg37 mice after 8 wpi (or 9 weeks of age in uninfected mice). Total transcript is reduced by ∼30%–40%, consistent with its absence within neurons in the hippocampus at this stage. The reduction is equivalent to the fraction of recombined DNA detected by Southern blotting previously described (Mallucci et al., 2002, Mallucci et al., 2003). RNA was pooled from five mice at each time point, and each reaction was performed in triplicate. Error bars represent standard deviation. Arrow indicates onset of Cre-mediated knockout.
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英文原文鏈接：http://www.neuron.org/content/article/fulltext?uid=PIIS0896627307000086
