EXCITATORY AMINO-ACID AMPA RECEPTOR MESSENGER-RNA LOCALIZATION IN SEVERAL REGIONS OF NORMAL AND NEUROLOGICAL DISEASE AFFECTED HUMAN BRAIN -AN IN-SITU HYBRIDIZATION HISTOCHEMISTRY STUDY

In situ hybridization histochemistry was used to localize the mRNAs co ding for four alpha-aminoisoxazole propionic acid-sensitive glutamate receptor subunits in human brain (age range 51-95 years, postmortem de lay 4.5-10 h). High levels of the B receptor subunit mRNA were present in all the studied regions, followed by the A-subunit and the C-subun it. Only very low levels of the D-subunit mRNA were detected. In hippo campus, the mRNA coding for the B-subunits of the glutamate receptor w as observed in granule cells of dentate gyrus and in the pyramidal cel ls of Ammon's horn. In cortex, the highest levels of glutamate recepto r subunit mRNAs were found in layer I and layers III-IV of entorhinal and temporal cortex, although significant levels were also observed in the other cell layers. A differential distribution was seen in cerebe llum where the A-subunit mRNA is expressed mainly by Purkinje cells, w hile the B-subunit mRNA is present in the internal granule cell layer. These results correlate well with previous data from autoradiographic studies on the localization of excitatory amino acid binding sites in human brain and pinpoint the cells where these receptors are synthesi zed. In situ hybridization in the hippocampus of patients affected by Alzheimer's disease (age range 77-82 years, postmortem delay 19-25.5 h ) revealed a decrease on the content of the mRNAs coding for these exc itatory amino acid receptors, while an increase was detected in surgic ally disected epileptic human hippocampi. These results corroborate an d extend the previous data from in vitro autoradiography and suggest a lteration of the excitatory amino acid disfunction during these neurod egenerative processes.