US EPA

2983627 

Journal Article 

Selective killing of cholinergic neurons by microglial activation in basal forebrain mixed neuronal/glial cultures 

Mcmillian, M; Kong, LY; Sawin, SM; Wilson, B; Das, K; Hudson, P; Hong, JS; Bing, G 

1995 

Yes 

Biochemical and Biophysical Research Communications
ISSN: 0006-291X
EISSN: 1090-2104 

215 

2 

572-577 

English 

7487994 

10.1006/bbrc.1995.2503 

WOS:A1995RZ36500021 

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.