Widespread reports of changes in RNA message abundance and specific RNA message levels in senescent cultured primary neural cells, in normal aging human brain and especially in Alzheimer’s disease-afflicted neocortex and hippocampus suggest the down-regulation of brain-specific genes during senescence, aging and in AD. To this end, a reduction in the general availability of transcription factors (TFs) and related signal transduction elements have been implicated in AD and age-related syndromes.
To further decipher changes in TF and signal transduction gene expression in AD hippocampus associated with brain aging and neurodegeneration, Lukiw et al. (301.6) simultaneously analyzed ~1200 RNA message levels using broad-spectrum commercially available cDNA array panels (Clontech part number 7852-1) and 32P-labeled cDNA probes derived from hippocampal CA1 poly A+ RNA fractions. RNA messages were isolated from a group of five pooled control and five pooled AD brains to aid in minimizing individual differences in brain gene expression patterns. Importantly, there were no significant differences in age, postmortem interval, drug or genetic history between the control and AD groups. The authors reported that AD samples showed significant decreases of threefold or more (each pSeven TF RNA message levels were found to be decreased in this study. Six (including GATA-4, BRCA1-associated, PCAF-associated 65B,LYL-1, MTF-1 and GATA-2) are known to be developmentally regulated and a different set of six required the trace element zinc (including the GATA group, LYL-1, MTF-1 and NF-KB p52). Interestingly, MTF-1, a metal regulatory element, is known to be essential in the response of the brain to potentially neurotoxic metal ion load. MTF-1 is also a major contributor to the redox state of the cell, and increases in the levels of reactive oxygen species in AD have been widely reported. In these experiments, the only TF that was found to be increased was one member of the nuclear factor-KB gene family, the NF-KB p52 subunit, which has an established role in the proliferation of the brain’s immune and inflammatory response.—Walter Lukiw
(Note: Dr. Lukiw is an author of this abstract.)
References: Abstract 301.6. Lukiw WJ, Carver LA, LeBlanc HJ, Bazan NG. Decreases in zinc-dependent transcription factor messenger RNA in Alzheimer's disease hippocampal CA1 region as analyzed by high density cDNA arrays.
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