Regional distribution of messenger RNAs in postmortem human brain

The ability to isolate intact RNAs from postmortem human brain permits analysis of gene expression and may help uncover the nature of the molecular lesions in neurological diseases. Starting with poly(A) RNA from postmortem brain of neurologically normal patients, we have constructed two complementary DNA libraries in the plasmid vector pBR322. Each of these libraries contains 2-3 X 10(4) recombinants. One library represents RNA species from the cerebellar cortex, the other from the neostriatum. Using differential colony hybridization, we identified more than 100 relatively abundant RNA species that appeared to be expressed in brain but not in liver. We then used 16 of these clones to analyze brain and liver RNAs by RNA blot hybridization. Thirteen of the 16 clones hybridized to RNAs of both liver and brain. One clone hybridized only to brain RNA, while seven hybridized to RNA species that were present at higher concentrations in brain than in liver. Eleven of the 16 clones hybridized to more than one species of RNA. None of the RNA species examined by RNA blot hybridization was limited to a single brain region, though seven of the cDNA clones hybridized to RNAs that were present at different concentrations in different regions. We have also examined the regional distribution of the RNA encoding glutamic acid decarboxylase, which catalyzes the production of gamma-aminobutyric acid (GABA). GAD RNA showed differential expression among brain regions and was not detectable in liver or kidney. Our data support a model of gene regulation that is based on cell identity, rather than regional specificity.