Cranial irradiation alters dendritic spine density and morphology in the hippocampus.

Cranial irradiation alters dendritic spine density and morphology in the hippocampus.
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DOI:
10.1371/journal.pone.0040844
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Fike JR
Fike JR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chakraborti A;Allen A;Allen B;Rosi S;Fike JR

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脑的治疗性照射是脑肿瘤的常见治疗方式,但可导致认知功能受损。树突棘是兴奋性突触传递的位点,棘结构和数量的变化被认为代表与海马依赖性学习和记忆相关的脑功能改变的形态学相关性。为了深入了解脑照射后海马的时间和亚区域特异性细胞变化,我们研究了10戈伊颅脑照射对年轻成年小鼠树突棘的影响。照射后1周或1个月,用高尔基体染色定量齿状回(DG)颗粒和CA 1锥体神经元棘密度和形态的变化。我们的结果表明,在DG中,在照射后1周(11.9%)和1个月(26.9%)时,脊柱密度均显著降低。与此相反,在CA1锥体神经元的基底树突,辐射导致在一个显着的减少(18.7%)的棘密度仅在1周后照射。棘形态学分析表明,照射导致在DG以及CA 1基底树突的蘑菇棘的比例在两个时间点显着下降。照射后1个月,两个区域的棘突比例均显著增加。辐射没有改变棘密度在CA 1顶树突,但有显着变化的比例薄,蘑菇棘在两个时间点后照射。虽然所涉及的机制尚不清楚,但这些发现首次表明,年轻成年动物的脑照射导致海马中树突棘密度和形态的变化,其变化具有时间依赖性和区域特异性。
Therapeutic irradiation of the brain is a common treatment modality for brain tumors, but can lead to impairment of cognitive function. Dendritic spines are sites of excitatory synaptic transmission and changes in spine structure and number are thought to represent a morphological correlate of altered brain functions associated with hippocampal dependent learning and memory. To gain some insight into the temporal and sub region specific cellular changes in the hippocampus following brain irradiation, we investigated the effects of 10 Gy cranial irradiation on dendritic spines in young adult mice. One week or 1 month post irradiation, changes in spine density and morphology in dentate gyrus (DG) granule and CA1 pyramidal neurons were quantified using Golgi staining. Our results showed that in the DG, there were significant reductions in spine density at both 1 week (11.9%) and 1 month (26.9%) after irradiation. In contrast, in the basal dendrites of CA1 pyramidal neurons, irradiation resulted in a significant reduction (18.7%) in spine density only at 1 week post irradiation. Analysis of spine morphology showed that irradiation led to significant decreases in the proportion of mushroom spines at both time points in the DG as well as CA1 basal dendrites. The proportions of stubby spines were significantly increased in both the areas at 1 month post irradiation. Irradiation did not alter spine density in the CA1 apical dendrites, but there were significant changes in the proportion of thin and mushroom spines at both time points post irradiation. Although the mechanisms involved are not clear, these findings are the first to show that brain irradiation of young adult animals leads to alterations in dendritic spine density and morphology in the hippocampus in a time dependent and region specific manner.
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