Cisplatin treatment induces attention deficits and impairs synaptic integrity in the prefrontal cortex in mice.
Cisplatin treatment induces attention deficits and impairs synaptic integrity in the prefrontal cortex in mice.
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DOI：
10.1038/s41598-018-35919-x
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发表时间：
2018-11-27
影响因子：
4.6
通讯作者：
Kavelaars A
中科院分区：
文献类型：
--
作者：
Huo X;Reyes TM;Heijnen CJ;Kavelaars A
接受癌症治疗的患者经常会出现化疗，其特征是记忆力受损和注意力下降。这些缺陷往往在治疗后持续存在，并且没有预防或治疗干预措施。在小鼠中，我们使用5选择系列反应时间任务评估顺铂化疗对注意力和突触完整性的影响。我们还评估了间充质干细胞的能力，以正常化的特性chemobrain。小鼠在5-选择系列反应时间任务中训练。在4秒刺激时间达到进展标准后，他们接受顺铂治疗，然后鼻腔给予间充质干细胞。顺铂降低了正确反应的百分比，由于遗漏的增加，表明注意力缺陷。间充质干细胞治疗逆转了这些顺铂诱导的注意力缺陷。顺铂还诱导前额叶皮层中突触完整性标记物的异常。具体而言，顺铂降低了整体突触前标记物突触素和突触能突触前标记物vGlut 2的表达。突触前GABA能标记物vGAT的表达增加。鼻腔间充质干细胞给药使这些突触完整性标志物正常化。总之，顺铂诱导持久的注意力缺陷，这与前额叶皮层突触完整性降低有关。经鼻给予间充质干细胞逆转了这些行为和结构缺陷。
Patients treated for cancer frequently experience chemobrain, characterized by impaired memory and reduced attention. These deficits often persist after treatment, and no preventive or curative interventions exist. In mice, we assessed the effect of cisplatin chemotherapy on attention using the 5-choice serial reaction time task and on synaptic integrity. We also assessed the capacity of mesenchymal stem cells to normalize the characteristics of chemobrain. Mice were trained in the 5-choice serial reaction time task. After reaching advancement criteria at a 4-second stimulus time, they were treated with cisplatin followed by nasal administration of mesenchymal stem cells. Cisplatin reduced the percentage of correct responses due to an increase in omissions, indicating attention deficits. Mesenchymal stem cell treatment reversed these cisplatin-induced deficits in attention. Cisplatin also induced abnormalities in markers of synaptic integrity in the prefrontal cortex. Specifically, cisplatin decreased expression of the global presynaptic marker synaptophysin and the glutamatergic presynaptic marker vGlut2. Expression of the presynaptic GABAergic marker vGAT increased. Nasal mesenchymal stem cell administration normalized these markers of synaptic integrity. In conclusion, cisplatin induces long-lasting attention deficits that are associated with decreased synaptic integrity in the prefrontal cortex. Nasal administration of mesenchymal stem cells reversed these behavioural and structural deficits.
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影响因子：
5.3
作者：
Adams, Michelle M.;Shi, Lei;Brunso-Bechtold, Judy K.
通讯作者：
Brunso-Bechtold, Judy K.
影响因子：
3.7
作者：
Donega V;van Velthoven CT;Nijboer CH;van Bel F;Kas MJ;Kavelaars A;Heijnen CJ
通讯作者：
Heijnen CJ
评估鼻内间充质干细胞治疗小鼠新生儿脑损伤的长期安全性和功效。
影响因子：
3.6
作者：
Donega V;Nijboer CH;van Velthoven CT;Youssef SA;de Bruin A;van Bel F;Kavelaars A;Heijnen CJ
通讯作者：
Heijnen CJ
影响因子：
7.4
作者：
Bittar A;Jun J;La JH;Wang J;Leem JW;Chung JM
通讯作者：
Chung JM
DOI：
10.3390/antiox6020025
发表时间：
2017-04-05
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Gao J;Wang L;Liu J;Xie F;Su B;Wang X
通讯作者：
Wang X