title: Thrombin-induced microglial activation contributes to the degeneration of nigral dopaminergic neurons in vivo.
abstract: OBJECTIVE
  To evaluate the role of thrombin-activated microglia in the neurodegeneration of nigral dopaminergic neurons in the rat substantia nigra (SN) in vivo.
  
  
  METHODS
  After stereotaxic thrombin injection into unilateral SN of rats, immunostaining, reverse transcription polymerase chain reaction (RT-PCR) and biochemical methods were used to observe tyrosine hydroxylase (TH) immunoreactive positive cells, microglia activation, nitric oxide (NO) amount and inducible nitric-oxide synthase (iNOS) expression.
  
  
  RESULTS
  (1) Selective damage to dopaminergic neurons was produced after thrombin injection, which was evidenced by loss of TH immunostaining in time-dependent manner; (2) Strong microglial activation was observed in the SN; (3) RT-PCR demonstrated the early and transient expression of neurotoxic factors iNOS mRNA in the SN. Immunofluorescence results found that thrombin induced expression of iNOS in microglia. The NO production in the thrombin-injected rats was significantly higher than that of controls (P < 0.05).
  
  
  CONCLUSIONS
  Thrombin intranigral injection can injure the dopaminergic neurons in the SN. Thrombin-induced microglia activation precedes dopaminergic neuron degeneration, which suggest that activation of microglia and release of NO may play important roles in dopaminergic neuronal death in the SN.
authors: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors: Cheng-Fang
authors: CF
authors: Huang
authors: Gang
authors: G
authors: Li
authors: Rong
authors: R
authors: Ma
authors: Sheng-Gang
authors: SG
authors: Sun
authors: Jian-Guo
authors: JG
authors: Chen
mesh_terms: D000818:Animals; D018450:Disease Progression; D004298:Dopamine / Q000096:biosynthesis; D004660:Encephalitis / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000633:toxicity; D007267:Injections; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013917:Thrombin / Q000633:toxicity*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D014446:Tyrosine 3-Monooxygenase; D013917:Thrombin; D004298:Dopamine