NGF-mediated alteration of NF-kappa B binding activity after partial immunolesions to rat cholinergic basal forebrain neurons

There are age-associated cognitive and cholinergic deficits in the neurotro phin-dependent cholinergic basal forebrain neurons (CBFNs). There are also increases in the activity of the transcription factor NF-kappa B in the age d rodent brain that may reflect chronic enhancement of stress response sign aling. We used partial immunolesions (PIL) to CBFN to examine the role of e ndogenous NGF on choline acetyltransferase (ChAT) activity and NGF-mediated NF-kappa B alteration after cholinergic deafferentation. We injected 192 I gG-saporin, an immunotoxin selectively taken up by neurotrophin receptor p7 5(NTR)-bearing neurons, into lateral ventricles, followed by infusions of a nti-NGF to assess NF-kappa B, ChAT and NGF responses to PIL after anti-NGF infusion. Treatment with anti-NGF decreased ChAT activity by 17-34% in the cortex, hippocampus, and olfactory bulb and PIL decreased ChAT activity by 47-73%. Changes in AChE activity levels paralleled those observed for ChAT after PIL. NGF protein levels in the olfactory bulb, but not the cortex or hippocampus, increased significantly after PIL treatment. Infusion of anti- NGF abolished the PIL-induced eight-fold NGF increase in CNS. NF-kappa B bi nding activity to the IgG-kappa B and ChAT specific NF-kappa B consensus se quences, increased in the cortex but not hippocampus after PIL followed by anti-NGF infusion. It is likely that immunolesion-induced changes in ambien t NGF levels may perturb NF-kappa B activity. (C) 2000 ISDN. Published by E lsevier Science Ltd. All rights reserved.