Long-term plastic changes in galanin innervation in the rat basal forebrain.

Galanin immunoreactive fibers hyperinnervate remaining cholinergic basal forebrain neurons in Alzheimer's disease, perhaps exacerbating the cholinergic deficit. The purpose of our study is to determine whether a similar phenomenon occurs following intraparenchymal injection of 192 IgG-saporin, a specific cholinergic neurotoxin, within the nucleus of the horizontal limb of the diagonal band of Broca. Immunotoxic lesion produced on average a 31% reduction in cholinergic cell counts ipsilateral to the lesion, compared to the contralateral side. Increased galanin immunoreactivity, suggestive of increased fiber density, was observed within and adjacent to the lesion in 28 out of 36 rats, and this effect persisted across time up to 6 months (the longest time examined). We observed a parallel increase in the number of galanin positive neurons ipsilateral to the lesion, compared to the contralateral side. No correlative change could be detected in the number of galaninergic neurons in the amygdala or the bed nucleus of the stria terminalis. There was no statistically significant correlation between the extent of cholinergic cell loss and the increase in galanin immunoreactivity surrounding the lesion. Yet, since both of these changes persist over time, we suggest that galanin plasticity is triggered by neuronal damage. Our model can be useful to test the role that galanin plays in the regulation of acetylcholine and the efficacy of galanin inhibitors as potential therapeutic interventions in Alzheimer's disease.