title: Three-Dimensional Electron Microscopy Reconstruction of Degenerative Dopaminergic Neurons Surrounded by Activated Microglia in Substantia Nigra.
abstract: There is an urgent need to investigate the reason for the pathogenic mechanism of intractable central neurological diseases such as Parkinson's disease. It has been reported that the activation of microglial cells is involved in the pathology of these diseases. However, due to technical difficulties, the relationship between degenerative neurons and activated microglial cells remains unclear. Therefore, we tried the improved analysis technique to clarify the spatial relationship between these cell types. We were able to establish an analysis technique that consists of a three-dimensional reconstruction method using serial immunoelectron micrographs after having identified both degenerative neurons and activated microglial cells under optical microscope. Using this technique, we have relatively easily been able to clarify the spatial relationship between degenerative neurons and activated microglial cells. Furthermore, using this technique it is possible to determine the neuronal degeneration process in detail, because it is able to identify structures implicated in degeneration, such as accumulation of lipofuscin in degenerated neuronal somata and phagocytotic structures of microglial cells. In future, this technical approach may be applied to elucidate the relationship between degenerative neurons and activated glial cells in human diseases.
authors.affiliation: a Department of Basic Science , Educational and Research Center for Pharmacy, Meiji Pharmaceutical University , Tokyo , Japan and.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakadate
authors.affiliation: b Department of Pharmacology and Toxicology , Dokkyo Medical University School of Medicine , Tochigi , Japan.
authors.forename: Sawako
authors.initials: S
authors.lastname: Tanaka-Nakadate
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000648:ultrastructure*; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D021621:Imaging, Three-Dimensional / Q000379:methods*; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000648:ultrastructure*; D046529:Microscopy, Electron, Transmission / Q000379:methods*; D016253:Microscopy, Immunoelectron / Q000379:methods; D009410:Nerve Degeneration / Q000473:pathology; D010300:Parkinson Disease / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000648:ultrastructure
keywords: Degeneration; immunoelectron microscopy; microglia activation; substantia nigra; three-dimensional reconstruction; transmission electron microscopy