title: Possible involvement of complement factor C1q in the clearance of extracellular neuromelanin from the substantia nigra in Parkinson disease.
abstract: Activation of the complement system promotes the removal of pathogens and tissue damage products from the brain and may also be involved in neuronal cell death in neurodegenerative diseases. Here, we analyzed the expression of C1q, the initial recognition subcomponent of the classic complement cascade, in the substantia nigra pars compacta (SNc) in Parkinson disease (PD) and control cases using immunohistochemistry and in situ hybridization. Microglia were determined to be the only cells that expressed C1q in the SNc and other brain areas. In the SNc of PD cases, there was increased deposition of extracellular neuromelanin in the parenchyma, resulting from degeneration of dopaminergic neurons. Neuromelanin granules and blebs of degenerated neurons seemed to be opsonized by C1q and phagocytosed by C1q-positive microglia and macrophages in the parenchyma and in the perivascular spaces. Neuromelanin-laden C1q-positive cells were also attached to the luminal surfaces of blood vessels in the SNc in PD. Thus, we present evidence suggesting that microglia are capable of phagocytosing and clearing cellular debris of degenerating neurons from the SNc through a C1q-mediated pathway in PD.
authors.affiliation: Experimental Neurology, Department of Neurology, Philipps University, Marburg, Germany.
authors.forename: Candan
authors.initials: C
authors.lastname: Depboylu
authors.forename: Martin K-H
authors.initials: MK
authors.lastname: Schäfer
authors.forename: Oscar
authors.initials: O
authors.lastname: Arias-Carrión
authors.forename: Wolfgang H
authors.initials: WH
authors.lastname: Oertel
authors.forename: Eberhard
authors.initials: E
authors.lastname: Weihe
authors.forename: Günter U
authors.initials: GU
authors.lastname: Höglinger
mesh_terms: D000368:Aged; D001344:Autopsy; D015922:Complement C1q / Q000502:physiology*; D004076:Digoxigenin; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007113:Immunity, Innate / Q000502:physiology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008543:Melanins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D010587:Phagocytosis; D013378:Substantia Nigra / Q000378:metabolism*; D016707:Tissue Fixation; D015854:Up-Regulation; D014544:Uridine Triphosphate
chemical_list: D008543:Melanins; C014121:neuromelanin; D015922:Complement C1q; D004076:Digoxigenin; D014544:Uridine Triphosphate