NMDA and AMPA receptors in transgenic mice expressing human beta-amyloid protein.
The human beta-amyloid protein may play an important, possibly primary, role in the pathogenesis of Alzheimer's disease (AD), and it appears to potentiate the susceptibility of neurons to excitotoxicity. AD is associated with alterations in the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtypes of glutamate receptors, and it has been suggested that excitotoxicity may play a role in neuronal damage in AD. In this study, we have used quantitative receptor autoradiography to examine NMDA and AMPA receptors in transgenic mice that contain the gene for the carboxyl-terminal 100 amino acids of the human amyloid precursor protein, beginning with the beta-amyloid region, which is under the control of the JC viral early region promoter. Reverse transcriptase-polymerase chain reaction confirmed that the brains of transgenic mice expressed beta-amyloid mRNA and that control mice did not. NMDA receptors, assessed with [3H]MK-801, were unchanged in the transgenic compared with the control mice. In the transgenic mice, there were no significant changes in [3H]AMPA receptor binding compared with controls. This study represents the first attempt to evaluate in transgenic mice the in vivo interaction between beta-amyloid expression and excitatory amino acid receptors.
Sandhu
F A
FA
Department of Biochemistry, University of Rochester School of Medicine, New York 14642.
Porter
R H
RH
Eller
R V
RV
Zain
S B
SB
Salim
M
M
Greenamyre
J T
JT
D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D017931:DNA Primers; D016291:Dizocilpine Maleate / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012016:Reference Values; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017931:DNA Primers; D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid