Differential vulnerability of primary cultured cholinergic neurons to nitric oxide excess

Many neuronal nitric oxide synthase (nNOS)-expressing brain neurons, includ ing some cholinergic populations, are resistant to disease or to certain fo rms of excitotoxicity. Vulnerability to NO excess of forebrain (medial sept al/diagonal band; MS-ACh) and brainstem (pedunculopontine/laterodorsal tegm ental nuclei; BS-ACh) cholinergic neurons was compared in E16-E18 primary r at brain cultures. MS-ACh cells were similar to 300-fold more sensitive to the NO donor S-nitro-N-acetyl-D,L-penicillamine (SNAP) than were BS-ACh cel ls. Most (69%) MS-ACh cells contained nuclear DNA fragments by 2 h after ad dition of SNAP, while only 21% BS-ACh cells were TUNEL-positive after NO ex cess. Depletion of glutathione content did not potentiate the effect of SNA P on MS-ACh cells, but sensitized BS-ACh cells to the NO donor. Caffeic aci d, a putative NF-kappa B inhibitor, enhanced the toxicity of SNAP to cholin ergic neurons in both preparations. Our experiments show that cholinergic n eurons in mixed primary cultures from different brain regions possess bioch emical differences with respect to their vulnerability to NO excess. NeuroR eport 11:931-936 (C) 2000 Lippincott Williams & Wilkins.