title: 6-Hydroxydopamine as a tool to understand adaptive immune system-induced dopamine neurodegeneration in Parkinson's disease.
abstract: BACKGROUND
  Neuroimmunological response is associated with neurodegeneration in the human substantia nigra (SN) in Parkinson's disease (PD).
  
  
  OBJECTIVE
  To explore the possibility that the neurotoxin, 6-hydroxydopamine (6-OHDA), could be used as a tool in mice to understand the immune response in PD.
  
  
  METHODS
  We employed unilateral administration of 6-OHDA into the mouse SN. At 1 week, 2 weeks and 4 weeks post-injection, we used immunohistochemistry for the markers Iba-1 and gp91PHOX to investigate activated microglia in the SN. To examine the adaptive immune response, we used immunohistochemistry for CD3-positive T-lymphocytes, CD45R-positive B-lymphocytes and anti-mouse immunoglobulin-G (IgG). Dopamine neuron loss was examined using immunohistochemistry for the dopamine neuron marker, tyrosine hydroxylase.
  
  
  RESULTS
  Compared to vehicle, 6-OHDA administration induced an intense IgG deposition in the SN as well as increased infiltration of both T- and B- lymphocytes into the injected side of the midbrain. The adaptive immune response was associated with extensive destruction of dopamine neurons and extensive microglial activation at every time point in the 6-OHDA groups.
  
  
  CONCLUSIONS
  Our results suggest that 6-OHDA administration in mice can a potential tool for understanding mechanisms underlying adaptive immune activation-induced neurodegeneration in PD.
authors.affiliation: McGuire Research Institute, Hunter Holmes McGuire Veteran Affairs Medical Center , Richmond, VA , USA .
authors.forename: Shaji
authors.initials: S
authors.lastname: Theodore
authors.forename: William
authors.initials: W
authors.lastname: Maragos
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016627:Oxidopamine / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000276:immunology* / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: C491049:Aif1 protein, mouse; D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D016627:Oxidopamine; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D017493:Leukocyte Common Antigens
keywords: Glia; immunoglobulins; lymphocytes; neuroimmunology; neurotoxin