TYROSINE KINASE-A, GALANIN AND NITRIC-OXIDE SYNTHASE WITHIN BASAL FOREBRAIN NEURONS IN THE RAT

Cholinergic basal forebrain neurons appear to play a key role in cogni tion and attention. In rat, basal forebrain neurons express multiple p roteins including the high-affinity signal transducing tyrosine kinase A receptor for nerve growth factor, the neuropeptide galanin and nitr ic oxide synthase, a marker for the novel neurotransmitter nitric oxid e. The present study was undertaken to define the relationship between neurons expressing each of these markers within the medial septum-ver tical limb of the diagonal band, horizontal limb of the diagonal band and nucleus basalis in colchicine pre-treated rats. Tyrosine kinase A- immunopositive neurons were seen throughout all subfields of the basal forebrain. In contrast, nitric oxide synthase- and galanin-immunoreac tive neurons were mainly distributed within the septal-diagonal band c omplex. Co-localization experiments revealed that virtually all nitric oxide synthase-positive neurons (visualized by nicotinamide adenine d inucleotide phosphate-diaphorase histochemistry) also contained tyrosi ne kinase A, whereas many fewer tyrosine kinase A neurons were nicotin amide adenine dinucleotide phosphate-diaphorase positive within the me dial septum-vertical limb of the diagonal band. Within the horizontal limb of the diagonal band, numerous nicotinamide adenine dinucleotide phosphate-diaphorase neurons expressed tyrosine kinase A, whereas only a small number of tyrosine kinase A neurons contained nicotinamide ad enine dinucleotide phosphate-diaphorase. Within the nucleus basalis ve ry few neurons were nicotinamide adenine dinucleotide phosphate-diapho rase reactive, and a minor number contained tyrosine kinase A. Additio nal co-localization experiments revealed minor percentages of neurons containing nicotinamide adenine dinucleotide phosphate-diaphorase and galanin immunoreactivity within the various subfields of the basal for ebrain. Within the horizontal limb of the diagonal band minor numbers of nicotinamide adenine dinucleotide phosphate-diaphorase-reactive per ikarya displayed galanin. Similarly, only a few galanin-containing neu rons expressed nicotinamide adenine dinucleotide phosphate-diaphorase. The existence of tyrosine kinase A, nitric oxide synthase and galanin within select neuronal subgroups of the cholinergic basal forebrain s uggests that these perikarya are responsive to a complex set of chemic al signals. A greater understanding of the chemical signature of the c holinergic basal forebrain neurons will provide the insight required t o develop novel pharmacological approaches aimed at preventing or slow ing the degenerative processes that effect these neurons in aging and pathologic disorders. (C) 1998 IBRO. Published by Elsevier Science Ltd .