title: Repeated immunolesions display diminished stress response signal.
abstract: Cholinergic basal forebrain neurons (CBFNs) retrogradely transport neurotrophins 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 spared 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 extent and mechanism of the endogenous stimulation of NGF in response to injury can be mimicked via treatment with 192 IgG-saporin of rat CNS, an immunolesion model. Here we report on the use of a conditioning lesion paradigm to 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 effective as a one time equivalent immunolesion in terms of induced NGF protein increases or decreasing ChAT and AChE activity in the hippocampus and cortex. Thus, chronic lesions resulting in cholinergic impairment typical of the aged CNS may differ from acute toxic models as a result of desensitization due to a conditioning effect of chronic subthreshold lesioning events in the CNS.
authors.affiliation: Department of Human Biological Chemistry, The University of Texas Medical Branch at Galveston, 301 University Blvd, Galveston, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Gu
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.forename: K
authors.initials: K
authors.lastname: Werrbach-Perez
authors.forename: J R
authors.initials: JR
authors.lastname: Perez-Polo
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis / Q000378:metabolism; D000222:Adaptation, Physiological / Q000187:drug effects* / Q000276:immunology; D000375:Aging / Q000502:physiology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D020532:Basal Nucleus of Meynert / Q000166:cytology; D002540:Cerebral Cortex / Q000166:cytology / Q000503:physiopathology*; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology*; D020667:Diagonal Band of Broca / Q000166:cytology; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D000922:Immunotoxins / Q000494:pharmacology*; D008297:Male; D009699:N-Glycosyl Hydrolases; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000032:analysis; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013312:Stress, Physiological / Q000276:immunology / Q000503:physiopathology*
chemical_list: C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D020800:Receptor, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D009699:N-Glycosyl Hydrolases; D000076985:Saporins