Repeated immunolesions display diminished stress response signal

Cholinergic basal forebrain neurons (CBFNs) retrogradely transport neurotro phins released in the hippocampus and cortex as part of a general response to injury in a process that is impaired in the aged rodent and can be spare d by the exogenous addition of pharmacological doses of nerve growth factor (NGF). This observation suggests that components of stress response signal transduction pathways in the aged CNS can be exogenously activated. The ex tent and mechanism of the endogenous stimulation of NGF in response to inju ry can be mimicked via treatment with 192 IgG-saporin of rat CNS, an immuno lesion model. Here we report on the use of a conditioning lesion paradigm t o determine if repeated partial immunolesions have a conditioning effect on the immunolesion-induced increases in NGF protein or decreases in choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity. We report that chronic repeated immunolesions, as used here, were not as ef fective as a one time equivalent immunolesion in terms of induced NGF prote in increases or decreasing ChAT and AChE activity in the hippocampus and co rtex. Thus, chronic lesions resulting in cholinergic impairment typical of the aged CNS may differ from acute toxic models as a result of desensitizat ion due to a conditioning effect of chronic subthreshold lesioning events i n the CNS. (C) 2000 ISDN, Published by Elsevier Science Ltd. All rights res erved.