Gu Z, Toliver-Kinsky T, Glasgow J, Cain L, Perez-Polo JR (1999) NGF-mediated alteration of NF-κB binding activity after partial immuno-lesions to rat cholinergic basal forebrain neurons. Neuroscience 1999 Abstracts 300.15. Society for Neuroscience, Miami, FL.
Summary: Memory loss and cognitive deficits in die aged and in patients with Alzheimer’s disease (AD) are often associated with cholinergic deficits within the NGF-dependent cholinergic basal forebrain neurons (CBFNs) that project to the cortex, hippocampus, and olfactory bulb. Although the causes of these cholinergic deficits are not fully understood, the increases in activity of the transcription factor NF-κB in the brains from aged and AD patient may reflect chronic transcription enhancement of stress response genes that affect cholinergic expression and neuronal death. In order to ascertain whether endogenous NGF effects on ChAT and NF-κB may account for recovery from stress, a partial immunolesion (PIL) to CBFNs, which is produced by the injection of 192 IgG-saporin, an immunotoxin selectively taken up by low-affinity NGF receptor p75NTR-bearing neurons, was conducted and followed by infusion of anti-NGF. Both PIL and anti-NGF treatment decreased ChAT activity in cortex, hippocampus, and olfactory bulb. NGF protein levels increased significantly in the olfactory bulb, but not the cortex or hippocampus after PIL treatment. Infusion of anti-NGF abolished the PIL-induced NGF increases in cerebrospinal fluid. We also found that NF-κB binding activity to both the κ light chain enhancer and the ChAT promoter specific consensus sequence increased in PIL-induced cortex but not hippocampus after anti-NGF infusion as measured by electrophoretic mobility shift assays (EMSAs). This is consistent with the hypothesis that NF-κB contributes as a repressor to the transcriptional regulation of ChAT by NGF. Taken together with reports of increased levels of NF-κB activity in brains of aged rats and of AD patients, it is likely that NGF-mediated changes in NF-κB activity in part reflect responses to age-associated cholinergic deficits. (Supported in part by NINDS Grant NS 33288)
Related Products: 192-IgG-SAP (Cat. #IT-01)