101. Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures.
- Author
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McMillian M, Kong LY, Sawin SM, Wilson B, Das K, Hudson P, Hong JS, and Bing G
- Subjects
- Amyloid beta-Peptides pharmacology, Animals, Arginine analogs & derivatives, Arginine pharmacology, Cell Survival drug effects, Cells, Cultured, Choline O-Acetyltransferase analysis, Coculture Techniques, Dizocilpine Maleate pharmacology, Embryo, Mammalian, Enzyme Induction drug effects, Interferon-gamma pharmacology, Lipopolysaccharides pharmacology, Microglia drug effects, Microglia metabolism, NG-Nitroarginine Methyl Ester, Neurons drug effects, Neurons metabolism, Nitric Oxide Synthase biosynthesis, Prosencephalon cytology, Prosencephalon metabolism, Rats, Recombinant Proteins, Cell Survival physiology, Choline O-Acetyltransferase metabolism, Microglia cytology, Neurons cytology
- Abstract
Microglia activation by lipopolysaccharides (LPS) significantly decreased choline acetyltransferase-immunopositive (ChAT+) neuron number and ChAT activity in rat primary basal forebrain mixed neuronal/glial cultures. The number of non-cholinergic (ChAT(-)) neurons was unaffected. LPS induced nitric oxide synthase (NOS) in microglia, increased the media level of the NO metabolite nitrite, and the NOS inhibitor Ng-nitro-L-arginine methylester (NAME) protected the ChAT+ neurons from LPS. The combination of beta-amyloid peptide (1-42) and interferon-gamma (INF-gamma) also increased the media nitrite level and decreased ChAT+ neuron number. Cholinergic neurons are lost early in the course of Alzheimer's disease, and the enhanced sensitivity of these neurons to microglial activation in mixed neuronal/glial culture may be useful for modeling Alzheimer's disease and developing therapeutic strategies to combat this disease.
- Published
- 1995
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