一项研究发现,颅脑照射——这是常用于治疗脑瘤的一种方法——会诱导小鼠大脑产生持久的结构变化。颅脑照射疗法有效地抢先阻止了脑癌的发展,并且改善了存活,但是它可能破坏健康的组织并导致认知的削弱。Vipan K. Parihar和Charles L. Limoli试图阐明辐射暴露如何削弱大脑功能,他们研究了辐射暴露对小鼠大脑的一个称为海马区的区域中的神经元的结构和连接的效应。这组作者让小鼠暴露在两种不同剂量的颅脑照射中,在1个月的这种治疗中,他们观察到了树突的分支、长度和区域对剂量依赖的减少。树突是神经元的突起,它接收和发送来自其他神经元的信号。这组科研人员还发现了被称为树突棘的树突突起在数量和密度上的由辐射诱导的减少。这组作者指出,这种与辐射有关的变化类似于许多在神经退行性疾病中所发现的变化。该研究揭示出了辐射可能会对海马区的神经元的结构的复杂性产生持久的有害作用。这组作者说,需要进行进一步的研究从而确定这种观察到的变化对接受脑癌放射性治疗的病人所造成的认知削弱的程度。(生物谷 Bioon.com)
生物谷推荐的英文摘要
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.