SELECTIVE KILLING OF CHOLINERGIC NEURONS BY MICROGLIAL ACTIVATION IN BASAL FOREBRAIN MIXED NEURONAL GLIAL CULTURES/

Microglia activation by lipopolysaccharides (LPS) significantly decrea sed choline acetyltransferase-immunopositive (ChAT+) neuron number and ChAT activity in rat primary basal forebrain mixed neuronal/glial cul tures. The number of non-cholinergic (ChAT(-)) neurons was unaffected. LPS induced nitric oxide synthase (NOS) in microglia, increased the m edia level of the NO metabolite nitrite, and the NOS inhibitor N-G-nit ro-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 ChATneuron number. Cholinergic neurons are lost early in the course of Alz heimer's disease, and the enhanced sensitivity of these neurons to mic roglial activation in mixed neuronal/glial culture may be useful for m odeling Alzheimer's disease and developing therapeutic strategies to c ombat this disease.