SHORT-TERM AND COMPLETE REVERSAL OF NGF EFFECTS IN RATS WITH LESIONS OF THE NUCLEUS BASALIS MAGNOCELLULARIS

Rats received bilateral quisqualic acid (QUIS) lesions of the nucleus basalis magnocellularis (NBM). Three weeks after lesioning, osmotic mi nipumps were implanted that released recombinant human nerve growth fa ctor (NGF) or cytochrome c at a dosage of 5.0 mu g rat(-1) day(-1) thr ough intracerebroventricular (ICV) cannulas for 7 weeks. One quarter o f the rats were sacrificed at the end of the treatment, while the rest of the animals were sacrificed 2, 8, and 12 weeks after termination o f NGF/cc treatment. ICV administration of NGF transiently reduced weig ht gain. NGF maximally increased choline acetyltransferase (ChAT) acti vity in all cortical regions, the olfactory bulb and the hippocampus b etween 20% and 56% at the end of the treatment. This increase linearly declined and completely regressed during the 12-week withdrawal perio d both in regions affected and unaffected by the lesion. Administratio n of NGF induced a short-lasting hypertrophy of low affinity NGF recep tor immunoreactive neurons within the nucleus basalis magnocellularis (NBM), the horizontal limb of the diagonal band of Broca, and the medi al septum (MS). In contrast, QUIS-induced NBM lesions permanently redu ced ChAT activity most pronounced in the frontal and parietal cortex u p to 45%. Furthermore, QUIS induced a permanent loss of p75NGFr-immuno reactive neurons within the NBM and the DB without affecting the MS. T hese findings suggest that degenerating cholinergic neurons of the NBM and HDB do not spontaneously recover after lesioning and may require continuous neurotrophic support by NGF to ameliorate cholinergic hypof unctioning. (C) 1998 Elsevier Science B.V.