TIME-COURSE OF CHANGES IN CHOLINERGIC AND NEUROTROPHIN-RELATED MARKERS AFTER INFUSION OF COLCHICINE INTO THE BASAL FOREBRAIN

After bilateral infusions of colchicine or vehicle in the rat nucleus basalis magnocellularis, the time course of changes in several choline rgic and neurotrophin-related markers were assessed. Animals were sacr ificed at 3, 7, 14, 28, 35 and 84 days post-lesion, and both the NBM a nd cortical areas were assessed. Sections were stained immunohistochem ically for choline acetyltransferase (ChAT) or p140(trk) (trk) or hist ochemically for acetylcholinesterase (AChE). ChAT activity and neurotr ophin protein levels were assessed regionally. The number of ChAT immu noreactive NBM neuronal profiles decreased beginning 3 days post-lesio n and reach maximal loss by 28 days post-lesion, with no recovery. Exa mination of trk-IR around the NBM revealed a time-dependent decrease i n trk-IR of magnocellular neurons and an increase in trk-IR of astrocy tes at 14 and 28 days post-lesion. The density of AChE-stained cortica l fibers was maximally decreased 3 days post-lesion followed by an inc rease in fiber staining across the remaining time points. Cortical ChA T activity showed the largest decrease at 7 days followed by recovery 84 days after colchicine infusion. There was an increase in NGF in the parietal cortex after colchicine infusion but no change in BDNF level . These patterns of changes in the cholinergic and neurotrophin-relate d markers suggest an association between NGF and lesion-induced compen satory responses in the basal forebrain cholinergic system. (C) 1998 E lsevier Science B.V.