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.
MeSH terms
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Amyloid beta-Peptides / pharmacology
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Animals
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Arginine / analogs & derivatives
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Arginine / pharmacology
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Cell Survival / drug effects
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Cell Survival / physiology*
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Cells, Cultured
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Choline O-Acetyltransferase / analysis
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Choline O-Acetyltransferase / metabolism*
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Coculture Techniques
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Dizocilpine Maleate / pharmacology
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Embryo, Mammalian
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Enzyme Induction / drug effects
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Interferon-gamma / pharmacology
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Lipopolysaccharides / pharmacology
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Microglia / cytology*
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Microglia / drug effects
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Microglia / metabolism
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NG-Nitroarginine Methyl Ester
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Neurons / cytology*
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Neurons / drug effects
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Neurons / metabolism
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Nitric Oxide Synthase / biosynthesis
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Prosencephalon / cytology
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Prosencephalon / metabolism
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Rats
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Recombinant Proteins
Substances
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Amyloid beta-Peptides
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Lipopolysaccharides
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Recombinant Proteins
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Dizocilpine Maleate
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Interferon-gamma
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Arginine
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Nitric Oxide Synthase
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Choline O-Acetyltransferase
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NG-Nitroarginine Methyl Ester