Immunohistochemical study of GABA(A) receptor beta2/3 subunits in the hippocampal formation of aged brains with Alzheimer-related neuropathologic changes.
In AD, it is hypothesized that one factor contributing to the vulnerability of neurons is a delicate balance of excitatory and inhibitory inputs. To examine this hypothesis we have initiated a number of studies examining the role of the excitatory neurotransmitter glutamate and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the neurodegeneration of AD. As an initial investigation into the GABAergic system in AD, we employed immunocytochemical techniques and examined the distribution and density of the GABAA receptor subunits beta2/3 within the hippocampus of 13 subjects with a clinical diagnosis of AD and 6 nondemented elderly subjects. Collectively, these 19 subjects presented with a broad range of pathologic severity (i.e., Braak stages I-VI). Density measurements of nine hippocampal regions demonstrated highest levels of beta2/3 immunolabeling in the inner molecular layer of the dentate gyrus > CA1 > CA2, while the lowest levels were found in the granular layer of the dentate gyrus < or = CA4 < CA3 field. Despite these regional variations no significant difference in the mean density of beta2/3 immunolabeling was observed when comparing the pathologically mild (stages I and II), moderate (stages III and IV), and severe (stages V and VI) groups. These data suggest that in the hippocampus receptor subunits associated with GABAergic neurotransmission are relatively maintained even until the terminal stages of the disease.
Mizukami
K
K
Neurosciences Research Center, Allegheny-Singer Research Institute, MCP and Hahnemann School of Medicine, Pittsburgh, Pennsylvania, USA.
Ikonomovic
M D
MD
Grayson
D R
DR
Rubin
R T
RT
Warde
D
D
Sheffield
R
R
Hamilton
R L
RL
Davies
P
P
Armstrong
D M
DM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000737:chemistry*; D016874:Neurofibrillary Tangles; D011487:Protein Conformation; D011963:Receptors, GABA-A / Q000032:analysis / Q000737:chemistry*; D017470:Receptors, Glutamate / Q000032:analysis
D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D017470:Receptors, Glutamate