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已发表论文
多柔比星给药后大鼠海马体内神经调节蛋白-1/ErbB 信号的转导异常
Authors Liao D, Guo Y, Xiang D, Dang R, Xu P, Cai H, Cao L, Jiang P
Received 12 September 2017
Accepted for publication 14 December 2017
Published 30 January 2018 Volume 2018:12 Pages 231—239
DOI https://doi.org/10.2147/DDDT.S151511
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 2
Editor who approved publication: Dr Qiongyu Guo
Objective: Long-term use
of doxorubicin (Dox) can cause neurobiological side effects associated with
depression, but the underlying mechanisms remain equivocal. While recent
evidence has indicated that Neuregulin-1 (NRG1) and its ErbB receptors play an
essential role in neural function, much is still unknown concerning the
biological link between the NRG1/ErbB pathway and the Dox-induced
neurotoxicity. Therefore, we examined the protein expression of NRG1 and ErbB
receptors in the hippocampus of rats following Dox treatment.
Materials and methods: The drug was administered every 2 days at a dose of 2.5 mg/kg, and the animals in different groups were treated with intraperitoneal injection for three or seven times, respectively.
Results: Our data showed that the rats treated with Dox for seven times (DoxL group) exhibited depression-like behaviors, whereas the short-term treatment (DoxS group) had no effect on the behavioral changes. Dox treatment also induced the neural apoptosis with more severe neurotoxicity. Intriguingly, the expression of NRG1 and the ratio of pErbB4/ErbB4 and pErbB2/ErbB2 were significantly decreased in the DoxL group, but enhanced activation of ErbB receptors was observed in the DoxS group. In parallel, administration of Dox for seven times suppressed the downstream Akt and ERK phosphorylation, while the Akt phosphorylation was enhanced with the administration of Dox for three times.
Conclusion: Our data first showed the Dox-induced alterations of the NRG1/ErbB system in the hippocampus, indicating the potential involvement of the NRG1/ErbB pathway in the Dox-induced nervous system dysfunction.
Keywords: chemotherapy, neurotoxicity, depression, NRG1/ErbB system, Akt, ERK
Materials and methods: The drug was administered every 2 days at a dose of 2.5 mg/kg, and the animals in different groups were treated with intraperitoneal injection for three or seven times, respectively.
Results: Our data showed that the rats treated with Dox for seven times (DoxL group) exhibited depression-like behaviors, whereas the short-term treatment (DoxS group) had no effect on the behavioral changes. Dox treatment also induced the neural apoptosis with more severe neurotoxicity. Intriguingly, the expression of NRG1 and the ratio of pErbB4/ErbB4 and pErbB2/ErbB2 were significantly decreased in the DoxL group, but enhanced activation of ErbB receptors was observed in the DoxS group. In parallel, administration of Dox for seven times suppressed the downstream Akt and ERK phosphorylation, while the Akt phosphorylation was enhanced with the administration of Dox for three times.
Conclusion: Our data first showed the Dox-induced alterations of the NRG1/ErbB system in the hippocampus, indicating the potential involvement of the NRG1/ErbB pathway in the Dox-induced nervous system dysfunction.
Keywords: chemotherapy, neurotoxicity, depression, NRG1/ErbB system, Akt, ERK
