MOLECULAR NEUROSCIENCEDifferential vulnerability of primary cultured cholinergic neurons to nitric oxide excessFass, Uwe1; Panickar, Kiran1; Personett, David1; Bryan, David1; Williams, Katrina1; Gonzales, John1; Sugaya, Kiminobu1; McKinney, Michael1,2Author Information 1Department of Pharmacology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL 32224, USA 2Corresponding Author: Michael McKinney Received 14 December 1999; accepted 20 January 2000 NeuroReport: April 7, 2000 - Volume 11 - Issue 5 - p 931-936 Buy Abstract Many neuronal nitric oxide synthase (nNOS)-expressing brain neurons, including some cholinergic populations, are resistant to disease or to certain forms of excitotoxicity. Vulnerability to NO excess of forebrain (medial septal/diagonal band; MSACh) and brainstem (pedunculopontine/laterodorsal tegmental nuclei; BS-ACh) cholinergic neurons was compared in E16-E18 primary rat brain cultures. MS-ACh cells were ∼300-fold more sensitive to the NO donor S-nitro-N-acetyl-D,L-penicillamine (SNAP) than were BS-ACh cells. Most (69%) MS-ACh cells contained nuclear DNA fragments by 2 h after addition of SNAP, while only 21% BS-ACh cells were TUNEL-positive after NO excess. Depletion of glutathione content did not potentiate the effect of SNAP on MS-ACh cells, but sensitized BS-ACh cells to the NO donor. Caffeic acid, a putative NF-KB inhibitor, enhanced the toxicity of SNAP to cholinergic neurons in both preparations. Our experiments show that cholinergic neurons in mixed primary cultures from different brain regions possess biochemical differences with respect to their vulnerability to NO excess. © 2000 Lippincott Williams & Wilkins, Inc.