中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2012, Vol. 7 ›› Issue (21): 1651-1658.

• 原著:颅神经损伤修复保护与再生 • 上一篇    下一篇

Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

  

  • 收稿日期:2012-03-29 修回日期:2012-06-06 出版日期:2012-07-25 发布日期:2012-07-25

Temporal profiles of synaptic plasticity-related signals in adult mouse hippocampus with methotrexate treatment

Miyoung Yang1, Juhwan Kim1, Sung-Ho Kim1, Joong-Sun Kim2, Taekyun Shin3, Changjong Moon1   

  1. 1  Department of Veterinary Anatomy, College of Veterinary Medicine and Animal Medical Institute, Chonnam National University, Gwangju 500-757, South Korea
    2  Department of Experimental Radiation, Research Center, Dongnam Institute of Radiological & Medical Sciences (DIRAMS), Busan 619-753, South Korea
    3  Department of Veterinary Anatomy, College of Veterinary Medicine, Jeju National University, Jeju 690-756, South Korea
  • Received:2012-03-29 Revised:2012-06-06 Online:2012-07-25 Published:2012-07-25
  • Contact: Changjong Moon, Ph.D., Associate professor, De-partment of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, 300 Yongbong-Dong, Buk-Gu, Gwangju 500-757, South Korea moonc@chonnam.ac.kr
  • About author:Miyoung Yang☆, D.V.M., Studying for doctorate, Department of Veterinary Anatomy, College of Veterinary Medicine, Chonnam National University, 300 Yongbong-Dong, Buk-Gu, Gwangju 500-757, South Korea.

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Abstract:

Methotrexate, which is used to treat many malignancies and autoimmune diseases, affects brain functions including hippocampal-dependent memory function. However, the precise mechanisms underlying methotrexate-induced hippocampal dysfunction are poorly understood. To evaluate temporal changes in synaptic plasticity-related signals, the expression and activity of N-methyl-D-aspartic acid receptor 1, calcium/calmodulin-dependent protein kinase II, extracellular signal-regulated kinase 1/2, cAMP responsive element-binding protein, glutamate receptor 1, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor were examined in the hippocampi of adult C57BL/6 mice after methotrexate (40 mg/kg) intraperitoneal injection. Western blot analysis showed biphasic changes in synaptic plasticity-related signals in adult hippocampi following methotrexate treatment. N-methyl-D-aspartic acid receptor 1, cal-cium/calmodulin-dependent protein kinase II, and glutamate receptor 1 were acutely activated during the early phase (1 day post-injection), while extracellular signal-regulated kinase 1/2 and cAMP responsive element-binding protein activation showed biphasic increases during the early  (1 day post-injection) and late phases (7–14 days post-injection). Brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor expression increased significantly during the late phase (7–14 days post-injection). Therefore, methotrexate treatment affects synaptic plasticity-related signals in the adult mouse hippocampus, suggesting that changes in synaptic plasticity-related signals may be associated with neuronal survival and plasticity-related cellular remodeling.

Key words: hippocampus, methotrexate, neurotrophic factor, synaptic plasticity-related signal, neural regeneration