GABA A receptor β2 and β3 subunits mRNA in the hippocampal formation of aged human brain with Alzheimer-related neuropathology

Abstract

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 γ-aminobutyric acid (GABA) neurotransmitter system as it participates in countering the neurotoxic effects of excessive glutamate receptor stimulation. Our previous studies demonstrate that β2/3 GABA A receptor subunit immunoreactivity is relatively well preserved in hippocampi with AD pathology. To further elucidate the molecular basis for this observation, we employed in situ hybridization histochemistry to examine the levels of β2 and β3 receptor subunit mRNAs in the hippocampus of 19 elderly subjects presenting with a broad range of pathologic severity (i.e., Braak stage I–VI). Semi-quantitative analysis with film autoradiograms revealed that β2 mRNA signal was highest in the granule cell layer, CA2 and CA1 subfields, while β3 mRNA hybridization was highest in the granule cell layer, followed by CA2≥CA3≥CA1 regions. No significant difference in β2 mRNA expression was detected among the pathologically mild, moderate or severe groups. In contrast, levels of β3 mRNA in the pathologically severe group was significantly decreased compared to the mild group within all subregions examined except CA4. Our data suggest that alterations in the expression of GABA A receptor subunits in the AD hippocampus differ between specific receptor subunits with the amount of β2 mRNA being relatively well-preserved, while β3 mRNA levels were decreased.