GABA(A) RECEPTOR BETA-2 AND BETA-3 SUBUNITS MESSENGER-RNA IN THE HIPPOCAMPAL-FORMATION OF AGED HUMAN BRAIN WITH ALZHEIMER-RELATED NEUROPATHOLOGY

Our work on the role of glutamate in Alzheimer's disease (AD)-related neuronal vulnerability and death provided significant insight into the potential contribution of the gamma-aminobutyric acid (GABA) neurotra nsmitter system as it participates in countering the neurotoxic effect s of excessive glutamate receptor stimulation. Our previous studies de monstrate that beta 2/3 GAB(A), receptor subunit immunoreactivity is r elatively well preserved in hippocampi with AD pathology. To further e lucidate the molecular basis for this observation, we employed in situ hybridization histochemistry to examine the levels of beta 2 and beta 3 receptor subunit mRNAs in the hippocampus of 19 elderly subjects pr esenting with a broad range of pathologic severity (i.e., Braak stage I-VI). Semi-quantitative analysis with film autoradiograms revealed th at beta 2 mRNA signal was highest in the granule cell layer, CA2 and C A1 subfields, while beta 3 mRNA hybridization was highest in the granu le cell layer, followed by CA2 greater than or equal to CA3 greater th an or equal to CA1 regions. No significant difference in beta 2 mRNA e xpression was detected among the pathologically mild, moderate or seve re groups. In contrast, levels of beta 3 mRNA in the pathologically se vere group was significantly decreased compared to the mild group with in all subregions examined except CA4. Our data suggest that alteratio ns in the expression of GAB(A), receptor subunits in the AD hippocampu s differ between specific receptor subunits with the amount of beta 2 mRNA being relatively well-preserved, while beta 3 mRNA levels were de creased. (C) 1998 Elsevier Science B.V.