Model for aging in the basal forebrain cholinergic system.
A key component of the cognitive deficits associated with aging is the loss of function of cholinergic neurons in the basal forebrain due to neuronal losses and decreased cholinergic function of spared neurons. A model to mimic one aspect of this phenomenon is to kill cholinergic neurons selectively in the basal forebrain via administration of the immunotoxin IgG-192-saporin. Here we discuss apoptotic regulators, such as nerve growth factor, in age-associated changes present in the cholinergic system and the role of the NF-kappaB signaling system in cellular commitment to apoptosis. We also examine the age-associated decline in intrinsic response mechanisms, which may account for the age-associated reduction in recovery from both acute and chronic insults to the central nervous system.
Gu
Z
Z
Department of Human Biological Chemistry and Genetics, The University of Texas Medical Branch at Galveston 77555-0652, USA.
Wortwein
G
G
Yu
J
J
Perez-Polo
J R
JR
D000375:Aging; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D018678:Cholinergic Agents / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology; D009699:N-Glycosyl Hydrolases; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000378:metabolism*; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D018678:Cholinergic Agents; D000922:Immunotoxins; D016328:NF-kappa B; D011950:Receptors, Cholinergic; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; D000076985:Saporins