Microglia-derived proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta induce Purkinje neuronal apoptosis via their receptors in hypoxic neonatal rat brain

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• 作者：Charanjit Kaur (1)
  Viswanathan Sivakumar (1)
  Zhirong Zou (3)
  Eng-Ang Ling (1)
  
• 关键词：Hypoxia ; Activated microglia ; Purkinje neurons ; Hypoxia ; inducible factor ; 1α ; Proinflammatory cytokines ; Nitric oxide ; TNF ; α/IL ; 1β receptors
• 刊名：Brain Structure and Function
• 出版年：2014
• 出版时间：January 2014
• 年：2014
• 卷：219
• 期：1
• 页码：151-170
• 全文大小：2,669 KB
• 作者单位：Charanjit Kaur (1)
  Viswanathan Sivakumar (1)
  Zhirong Zou (3)
  Eng-Ang Ling (1)
  
  1. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Blk MD10, 4 Medical Drive, Singapore, 117597, Singapore
  3. Department of Anatomy, Faculty of Basic Medical Sciences, Kunming Medical University, 1168 West Chunrong Road, Kunming, 650500, People’s Republic of China
  
• ISSN：1863-2661

文摘

The developing cerebellum is extremely vulnerable to hypoxia which can damage the Purkinje neurons. We hypothesized that this might be mediated by tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) derived from activated microglia as in other brain areas. One-day-old rats were subjected to hypoxia following, which the expression changes of various proteins in the cerebellum including hypoxia inducible factor-1α, TNF-α, IL-1β, TNF-R1 and IL-1R1 were analyzed. Following hypoxic exposure, TNF-α and IL-1β immunoexpression in microglia was enhanced coupled by that of TNF-R1 and IL-1R1 in the Purkinje neurons. Along with this, hypoxic microglia in vitro showed enhanced release of TNF-α and IL-1β whose receptor expression was concomitantly increased in the Purkinje neurons. In addition, nitric oxide (NO) level was significantly increased in the cerebellum and cultured microglia subjected to hypoxic exposure. Moreover, cultured Purkinje neurons treated with conditioned medium derived from hypoxic microglia underwent apoptosis but the incidence was significantly reduced when the cells were treated with the same medium that was neutralized with TNF-α/IL-1β antibody. We conclude that hypoxic microglia in the neonatal cerebellum produce increased amounts of NO, TNF-α and IL-1β which when acting via their respective receptors could induce Purkinje neuron death.