Thrombin-Induced Microglial Activation Produces Degeneration of Nigral Dopaminergic NeuronsIn Vivo

• DOI: 10.1523/jneurosci.23-13-05877.2003
• Publication Date: 2018-04-13T22:30:28Z
• Authors: Sang-H. Choi; Eun H. Joe; Seung U. Kim; Byung K. Jin
• Keywords: Neurons; 0301 basic medicine; Microinjections; Dopamine; Nitric Oxide Synthase Type II; Cell Count; Immunohistochemistry; Rats; Isoenzymes; Rats, Sprague-Dawley; 03 medical and health sciences; Parkinsonian Disorders; Cyclooxygenase 2; Prostaglandin-Endoperoxide Synthases; Disease Progression; Animals; Cytokines; Female; Microglia; Enzyme Inhibitors; Mitogen-Activated Protein Kinases; Nitric Oxide Synthase

The present study examined whether thrombin-induced microglial activation could contribute to death of dopaminergic neurons in the rat substantia nigra (SN) vivo. Seven days after thrombin injection into SN, tyrosine hydroxylase immunohistochemistry showed a significant loss nigral neurons. In parallel, thrombin-activated microglia, visualized by immunohistochemical staining using antibodies against complement receptor type 3 (OX-42) and major histocompatibility complex class II antigens were also observed where degeneration was found. Reverse transcription PCR at various time points demonstrated that activated microglia vivo exhibited an early transient expression inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), several proinflammatory cytokines, including interleukin 1beta (IL-1beta), IL-6, tumor necrosis factor alpha. Western blot analysis double-label increase iNOS COX-2 colocalization these proteins within microglia. SN partially inhibited NG-nitro-L-arginine methyl ester hydrochloride, NOS inhibitor, DuP-697, inhibitor. Additional studies extracellular signal-regulated kinase 1/2 (ERK1/2) p38 mitogen-activated protein (MAPK) as 30 min injection, kinases localized Inhibition ERK1/2 MAPK reduced mRNA rescued SN. results strongly suggest triggered endogenous compound(s) such may be involved neuropathological processes neuronal cell occur Parkinson's disease.