LONG-TERM CHANGES IN BRAIN CHOLINERGIC MARKERS AND NERVE GROWTH-FACTOR LEVELS AFTER PARTIAL IMMUNOLESION

There are deficits in cholinergic basal forebrain neurons (CBFNs) in t he aged brain and patients suffering Alzheimer's disease associated wi th a partial loss of the CBFNs. To mimic this partial loss and assess its long term effects on residual cholinergic activity and resultant t arget-derived nerve growth factor (NGF) levels, we produced a partial immunolesion to CBFNs with 192 IgG-saporin, an immunotoxin selectively taken up by p75(NTR)-bearing neurons. We measured two cholinergic mar kers, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, and NGF protein levels at 10 days, 1, 6 and 12 months postl esion. There were no significant changes in the cholinergic markers an d the NGF protein levels in the sham-treated animal controls during th e one year experiment. Ten days after 192 IgG-saporin treatment, ChAT activity decreased to 35-50% of controls in the olfactory bulb, hippoc ampus, and cortex. There was a minor but significant recovery of ChAT activity one year after the immunolesion in the hippocampus. Changes i n AChE activity mirrored the ChAT changes but were less robust. There were transient increases in NGF protein levels in the hippocampus and cortex that returned to basal levels at 6 months and 12 months postles ion, respectively. In summary, partial immunolesions resulted in parti al region-specific and time-dependent recoveries of cholinergic activi ty in the target areas of the basal forebrain after a partial eliminat ion of CBFNs and a return to basal levels of NGF protein consistent wi th the hypothesis that the remaining CBFNs compensated for losses of C hAT and NGF due to changes in cholinergic innervation of basal forebra in target areas. (C) 1998 Elsevier Science B.V. All rights reserved.