Age-related neural degeneration in nuclear-factor kappaB p50 knockout mice.
Nuclear factor-kappaB is a transcription factor that regulates a variety of genes involved not only with immune and inflammatory responses, but also in cell survival. Nuclear-factor kappaB in the CNS is an area of current research interest; however, its role in age-related neural degeneration is obscure. The present study examines developmental degeneration changes in wild type and nuclear factor-kappaB p50 subunit knockout mice (p50-/-) using various morphological methodologies. P50-/- mice appeared normal at birth. At 6 and 10 months old, the body weight of p50-/- mice was significantly less than that of wild type mice and they started to die from aging. Consistently, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling positive cells in the cortex were significantly more in p50-/- mice than that in wild type mice, and neuronal cells in the cortex, hippocampus and caudate nucleus-putamen decreased in p50-/- mice. Fewer myelinated axons of the optic nerve were found in p50-/- mice than in wild type mice at 6 months. In p50-/- mice, morphological examinations showed: 1) aging and degenerative changes in the cortex and hippocampus including increased lipofuscin granules in neural cytoplasm, 2) abnormal capillaries, 3) dark and watery alterations and organelle accumulations, 4) apoptotic glia cells, and 5) terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling and caspase-3 positive neurons. These results suggest that nuclear-factor kappaB may play an important role in neurovascular development, cell survival, and the aging process in the CNS. This new evidence linking nuclear-factor kappaB to myelination and aging may be of considerable importance for several areas of basic and clinical neuroscience.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, 165 Ashley Avenue, Charleston, SC 29425, USA.
Z-Y
ZY
Lu
S P
SP
Yu
J-F
JF
Wei
L
L
Wei
D000375:Aging; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D052002:NF-kappa B p50 Subunit / Q000172:deficiency*; D009410:Nerve Degeneration / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology
D052002:NF-kappa B p50 Subunit