title: Amyloid beta protein deposition and neuron loss in osteopetrotic (op/op) mice.
abstract: Formation of senile plaques (SPs) by amyloid beta (Abeta) protein is a neuropathological change which characterizes Alzheimer's disease (AD), and Abeta deposition and neuron loss are essential for the pathological cascade of the disease. Although the mechanism of Abeta deposition remains unclear, it has been suggested that clearance of Abeta protein may be impaired in the AD brain. Previous studies demonstrated that microglia were able to remove Abeta by releasing a metalloprotease or by phagocytosis, suggesting that microglia may play an important role in preventing Abeta deposition in the central nervous system (CNS). On the other hand, it was reported that the number of microglia was reduced in osteopetrotic (op/op) toothless mice resulting from the lack of functional macrophage colony-stimulating factor (M-CSF). The present study was thus designed to examine the Abeta deposition and the number of hippocampal neurons in the brain of op/op mice. A number of fibrillar plaques were detected in the cerebral cortex, hippocampus, amygdala and hypothalamus in op/op mice, however, no quantitative evidence of Abeta deposition was observed in normal mice. Moreover, the total number of pyramidal cells in the hippocampal CA1, and CA3 regions was significantly reduced in op/op mice when compared to the controls. These results demonstrate that Abeta deposition influence neuron loss and it may be suspected that expression of SPs may be in part regulated by microglia under physiological conditions.
authors: Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University, Graduate School of Biomedical Science, 1-2-3 Kasumi, Hiroshima 734-8553, Minami, Japan.
authors: Masato
authors: M
authors: Kaku
authors: Keisuke
authors: K
authors: Tsutsui
authors: Masahide
authors: M
authors: Motokawa
authors: Toshitsugu
authors: T
authors: Kawata
authors: Tadashi
authors: T
authors: Fujita
authors: Shinya
authors: S
authors: Kohno
authors: Yuiko
authors: Y
authors: Tohma
authors: Junji
authors: J
authors: Ohtani
authors: Kaoru
authors: K
authors: Tenjoh
authors: Kazuo
authors: K
authors: Tanne
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D010022:Osteopetrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D016173:Macrophage Colony-Stimulating Factor