一項研究發(fā)現(xiàn),,顱腦照射——這是常用于治療腦瘤的一種方法——會誘導(dǎo)小鼠大腦產(chǎn)生持久的結(jié)構(gòu)變化。顱腦照射療法有效地?fù)屜茸柚沽四X癌的發(fā)展,,并且改善了存活,,但是它可能破壞健康的組織并導(dǎo)致認(rèn)知的削弱。Vipan K. Parihar和Charles L. Limoli試圖闡明輻射暴露如何削弱大腦功能,,他們研究了輻射暴露對小鼠大腦的一個稱為海馬區(qū)的區(qū)域中的神經(jīng)元的結(jié)構(gòu)和連接的效應(yīng),。這組作者讓小鼠暴露在兩種不同劑量的顱腦照射中,在1個月的這種治療中,,他們觀察到了樹突的分支,、長度和區(qū)域?qū)┝恳蕾嚨臏p少,。樹突是神經(jīng)元的突起,,它接收和發(fā)送來自其他神經(jīng)元的信號。這組科研人員還發(fā)現(xiàn)了被稱為樹突棘的樹突突起在數(shù)量和密度上的由輻射誘導(dǎo)的減少,。這組作者指出,,這種與輻射有關(guān)的變化類似于許多在神經(jīng)退行性疾病中所發(fā)現(xiàn)的變化。該研究揭示出了輻射可能會對海馬區(qū)的神經(jīng)元的結(jié)構(gòu)的復(fù)雜性產(chǎn)生持久的有害作用,。這組作者說,,需要進行進一步的研究從而確定這種觀察到的變化對接受腦癌放射性治療的病人所造成的認(rèn)知削弱的程度。(生物谷 Bioon.com)
生物谷推薦的英文摘要
PNAS 10.1073/pnas.1307301110
Cranial irradiation compromises neuronal architecture in the hippocampus
Vipan Kumar Parihar and Charles L. Limoli
Cranial irradiation is used routinely for the treatment of nearly all brain tumors, but may lead to progressive and debilitating impairments of cognitive function. Changes in synaptic plasticity underlie many neurodegenerative conditions that correlate to specific structural alterations in neurons that are believed to be morphologic determinants of learning and memory. To determine whether changes in dendritic architecture might underlie the neurocognitive sequelae found after irradiation, we investigated the impact of cranial irradiation (1 and 10 Gy) on a range of micromorphometric parameters in mice 10 and 30 d following exposure. Our data revealed significant reductions in dendritic complexity, where dendritic branching, length, and area were routinely reduced (>50%) in a dose-dependent manner. At these same doses and times we found significant reductions in the number (20–35%) and density (40–70%) of dendritic spines on hippocampal neurons of the dentate gyrus. Interestingly, immature filopodia showed the greatest sensitivity to irradiation compared with more mature spine morphologies, with reductions of 43% and 73% found 30 d after 1 and 10 Gy, respectively. Analysis of granule-cell neurons spanning the subfields of the dentate gyrus revealed significant reductions in synaptophysin expression at presynaptic sites in the dentate hilus, and significant increases in postsynaptic density protein (PSD-95) were found along dendrites in the granule cell and molecular layers. These findings are unique in demonstrating dose-responsive changes in dendritic complexity, synaptic protein levels, spine density and morphology, alterations induced in hippocampal neurons by irradiation that persist for at least 1 mo, and that resemble similar types of changes found in many neurodegenerative conditions.