X-ray irradiation promotes apoptosis of hippocampal neurons through up-regulation of Cdk5 and p25

Cancer Cell International

Ya-Wei Yuan¹  Qiong Xia⁵  Que-Ling Liu²  Yong-Qing Han³  Chuan-Gang Li⁴  Ai-Min Sun¹ 

[1]Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China

[2]Current Affiliation: Department of Oncology, Second Hospital, Nanchang University Medical College, Nanchang, Jiangxi, China

[3]Current Affiliation: Department of Oncology, Shangrao People's Hospital, Shangrao, Jiangxi, China

[4]Department of Ultrasound Diagnosis, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

[5]Medical Imaging, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

关键词: Hippocampus;    Irradiation;    Apoptosis;    p25;    p35;    Cdk5;   

Others  :  793826
DOI  :  10.1186/1475-2867-13-47

 received in 2013-02-03, accepted in 2013-04-14,  发布年份 2013

【 摘 要 】

Background

Cranial radiation therapy has been used for the treatment of primary and metastatic brain tumors. A prominent feature of brain injury induced by the radiation therapy is hippocampal dysfunction, characterized by a decline in memory. Cdk5 plays an important role in memory formation. Abnormal Cdk5 activity is associated with neuronal apoptosis induced by neurotoxic stimuli. However, the roles of Cdk5 in hippocampal apoptosis in response to X-ray irradiation have not been explored.

Methods

The expression of Cdk5 activators, p35 and p25, in hippocampal neurons was tested in both in vivo animal and in vitro couture after X-ray irradiation.

Results

After X-ray irradiation at 20 Gy and 30 Gy in rats, the number of hippocampal neuronal pyknosis was increased, but the number of hippocampal neuron was decreased, in the hippocampal CA1 region of rats. In these animals undergone with X-ray irradiation, the expression of p35 was significantly down-regulated, but it was up-regulated in p25. These opposite expressions were also shown in the primary cultured hippocampal neurons with 30 Gy irradiation. The apoptosis induced by X-ray irradiation were significantly prevented by the pretreatment of Cdk5 inhibitor, roscovitine, in both in vivo and in vitro settings.

Conclusions

X-ray irradiation resulted in a hippocampal neuronal apoptosis through up-regulation of p25, the Cdk5 activator. Hyperactivity of Cdk5 was involved in the pathogenesis of X-ray irradiation-induced hippocampal neuronal apoptosis. Blockade of Cdk5 signal pathway effectively protected neurons from the irradiation-induced brain injury.

【 授权许可】

   
2013 Sun et al.; licensee BioMed Central Ltd.

【 图 表 】

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