Cortical peroxynitration of nerve growth factor in aged and cognitively impaired rats.
Basal forebrain cholinergic neurons (BFCN), a system involved in learning and memory processes, are highly dependent on a continuous supply of biologically active nerve growth factor (NGF). Age-related cholinergic atrophy and cell loss in normal brains is apparently not complemented by reductions in the levels of NGF as could be expected. In the present work, cortical proNGF/NGF were immunoprecipitated from cortical brain homogenates from young and aged and behaviorally characterized rats and resolved with antinitrotyrosine antibodies to reveal nitration of tyrosine residues in proteins. Cortical proNGF in aged and cognitively impaired rats was found to be a target for peroxynitrite-mediated oxidative damage with correlative impact on decrease in choline acetyltransferase activity. These studies provide evidence for oxidative stress damage of NGF molecules in the cerebral cortex of cognitively impaired aged rats as previously shown in AD human brains.
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Martin A
MA
Bruno
A Claudio
AC
Cuello
D000367:Age Factors; D000375:Aging; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000473:pathology*; D047468:Immunoprecipitation; D008297:Male; D018782:Maze Learning / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000502:physiology; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D009414:Nerve Growth Factors; D011498:Protein Precursors; C489226:pro-nerve growth factor, mouse; C002744:3-nitrotyrosine; D014443:Tyrosine; D010958:Plasminogen; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D010959:Tissue Plasminogen Activator