A possible model of senile plaques using synthetic amyloid beta-protein and rat glial culture.
The senile plaque (SP) is one of the pathological hallmarks in the brains of patients with Alzheimer's disease (AD), but the mechanism of its formation and its role in AD progression are not yet fully understood. Synthetic amyloid beta-protein (Abeta)1-40 is known to aggregate in vitro, and the aggregated Abeta has been widely used for in vitro experiments, in which its peculiar effects on neuronal and glial cells have been shown. To date, however, the formation of a SP-like structure in a culture system using synthetic Abeta has not been demonstrated. In this study, we established a possible SP model using synthetic Abeta1-40 and rat glial cultures as follows: (1) large spherical aggregates of synthetic Abeta (sAmys) were produced from synthetic Abeta1-40 (10-50 microm in diameter), (2) the sAmys were added to a glial culture, and (3) the characteristics of the sAmys and the reactions of glial cells (microglia and astrocytes) around the sAmys were analyzed. We found that the sAmys exhibited the same features as the dense amyloid core in SPs, including the intense green birefringence under polarized light with Congo red, and induced reactive features in glial cells, including induction of major histocompatibility complex class II antigen in the microglia and interleukin-1beta in the astrocytes, similar to those seen in SPs in the brain in AD. Given our findings, we consider that this glial culture system with the sAmys is a possible in vitro SP model and useful for investigating the effects of massive amyloid deposition on neuronal and glial cells.
Isobe
I
I
Department of Dementia Research, National Institute for Longevity Sciences, 36-3 Gengo, Morioka, Obu, Aichi, 474-8522, Japan.
Yanagisawa
K
K
Michikawa
M
M
D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D052160:Benzothiazoles; D002478:Cells, Cultured; D004396:Coloring Agents; D003224:Congo Red; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007091:Image Processing, Computer-Assisted; D007375:Interleukin-1 / Q000032:analysis; D017628:Microglia / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D058225:Plaque, Amyloid / Q000737:chemistry / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D004396:Coloring Agents; D005904:Glial Fibrillary Acidic Protein; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T; D003224:Congo Red; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat