›› 2009, Vol. 40 ›› Issue (5): 732-736.doi: 10.3969/j.issn.0529-1356.2009.05.008

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Neurotoxic effects of inflammation on dopaminergic neurons in the substantia nigra in the rhesus

  

  1. Beijing Institute for Neuroscience,Capital Medical University,Beijing Center of Neural Regeneration and Repairing,Key Laboratory for Neurodegenerative Diseases of the Ministry of Education,Beijing 100069,China
  • Received:2009-02-16 Revised:2009-04-14 Online:2009-10-06
  • Contact: ZHANG Jin-lu

Abstract: Objective To observe the neurodegenerative effects of inflammation, induced by intra-cerebral injection of lipopolysaccharide (LPS) on dopaminergic neurons in the substantia nigra of rhesus mI>onkey/I>, in order to explore the relations of mechanism of Parkinsonism with activation of microglia and the releasing of inflammatory factors in the animal brain. Methods Eight adult rhesus mI>onkey/I>s were divided into an acute experimental group and a chronic experimental group. Among them 3 mI>onkey/I>s were used for acute experiment. They were unilaterally injected with LPS and survived for 1 week to demonstrate the changes of tyrosine hydroxylase(TH) expression and inflammatory factor release by Western blotting analysis. The other 5 mI>onkey/I>s were used for chronic experiment and 4 of them were intranigrally injected with LPS and survived for 24 weeks and 48 weeks respectively after the injection. Only one mI>onkey/I> was injected with saline as a control animal. The injections were stereotaxically made 3 times(at weeks 0,8,16 respectively) in the substantia nigra on one side. The number of TH-positive neurons was detected by TH immunohistochemistry and the nigro-striatal levels of neurotransmitters were determined by high pressure liquid chromatogram (HPLC). Result In the acute experimental group of mokeys: no obvious changes of TH expressing could be seen either on the injection side and control side, but it was shown the activation of microglia and increasing expression of HLA-DR TNF-α,IL-1β and COX-2 in the substantia nigra on injected side. In the chronic experimental group of mokeys, however, the number of TH-positive neurons in the injected substantia nigra and neurotransmitters levels in the nigro-striatal area were decreased. No obvious changes could be seen in the control case of saline injected mI>onkey/I>. Conclusion LPS injection in the substantia nigra of the primate causes severe inflammation in one week, which may lead to a

Key words: Lipopolysaccharide, Substantia nigra, Inflammatory factor, Neurotransmitter, Immunohistochemistry, Western blotting, HPLC, Rhesus

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