Glutamate receptor dysregulation in the hippocampus of transgenic mice carrying mutated human amyloid precursor protein.
Alzheimer's disease transgenic mice overexpressing human amyloid precursor protein (hAPP) with the Swedish double mutation (hAPP(Sw)) develop age-related amyloid deposition and behavioral and electrophysiologic changes by an unknown mechanism. Analysis of glutamatergic receptor subtypes in 4- and 15-month-old heterozygous hAPP(Sw) transgenic mice revealed a selective increase in AMPA receptor binding in the hippocampus of 15-month-old transgenic mice, which have established cortical and hippocampal amyloid deposits. There were no significant alterations of GluR1, GluR2, and GluR4 protein expression by semiquantitative confocal analysis or GluR1 mRNA by in situ hybridization. There was no significant alteration in NMDA, in group I and II metabotropic glutamate and in muscarinic receptor binding, or in striatal dopamine and adenosine receptor binding in 15-month-old mice. These data suggest that mutant APP overexpression or age-related amyloid deposition produce a subtle specific alteration in hippocampal glutamate receptors with aging.
Cha
J H
JH
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Farrell
L A
LA
Ahmed
S F
SF
Frey
A
A
Hsiao-Ashe
K K
KK
Young
A B
AB
Penney
J B
JB
Locascio
J J
JJ
Hyman
B T
BT
Irizarry
M C
MC
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002802:Cholinesterases / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D018091:Receptors, AMPA; D011954:Receptors, Dopamine; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D018047:Receptors, Purinergic P1; D002802:Cholinesterases