Expression of superoxide dismutase messenger RNA in adult rat brain cholinergic neurons

Superoxide dismutase (SOD) protects cells exposed to an excess of the free radical nitric oxide, by preventing the formation of peroxynitrite. Certain central cholinergic neurons express constitutive nitric oxide synthase (nN OS), and presumably they are at risk from peroxynitrite intoxication. Immun ocytochemistry for choline acetyltransferase (ChAT) was combined with in si tu hybridization histochemistry (ISHH) to examine whether brain cholinergic populations differ with respect to their expression of the messenger RNA m olecules (mRNAs) for the manganese-dependent (Mn-SOD) and copper/zine-depen dent superoxide dismutases (Cu/Zn-SOD). The cholinergic neurons located in the reticular formation of the upper bra instem (the laterodorsal tegmental nucleus [LDTN] and the pedunculopontine nucleus [PPN]) were found to express relatively high levels of Mn-SOD mRNA, whereas cholinergic neurons located in the basal forebrain (substantia inn ominata [SI], diagonal band [DB], medial septum [MS], and the nucleus basal is magnocellularis [nBM]), and the striatal cholinergic interneurons expres sed low to intermediate levels of Mn-SOD mRNA. The rank order of median Mn- SOD mRNA density per cholinergic cell was LDTN > PPN > SI > striatum = nBM = DB > MS. This is similar to the rank order of nNOS mRNA densities in the cholinergic cells in these regions (R = 0.9, p < 0.02). The rank order of C u/Zn-SOD mRNA levels in cholinergic populations (DB > LDTN = PPN =MS > SI = nBM = striatum) was not correlated with nNOS mRNA (R = 0.29, P > 0.05). Th us, for cholinergic neurons, Mn-SOD may be important for protection from NO -related oxidative stress.