Amyloid-beta injection in rat amygdala alters tau protein but not mRNA expression.
Previously we demonstrated local and distant changes in tau protein immunoreactivity reminiscent of those seen in Alzheimer's disease (AD) following a unilateral injection of amyloid-beta (Abeta)(25-35) into the rat amygdala. To explore the relevance of these findings to AD, we compared the effects of Abeta(1-42) to those of Abeta(25-35). Injections of both Abeta(1-42) and Abeta(25-35) into rat amygdala resulted in increased tau-2 immunolabeling in neurons. To determine whether these alterations were due to changes in the expression of tau, we measured tau protein expression by Western blotting and tau mRNA isoform expression by the reverse transcription-polymerase chain reaction in the amygdala, hippocampus, and cerebellum following a unilateral injection of Abeta(25-35) or vehicle into the amygdala. The levels of tau proteins were increased bilaterally in the amygdala of Abeta(25-35)- compared to vehicle-treated animals 8 and 16 days following treatment. The molecular weights of tau proteins were decreased in the Abeta(25-35)-treated (59-69 kDa) compared to the vehicle-treated (67-72 kDa) animals 8 days following treatment. There were no changes in tau mRNA expression in any brain region examined. In this model, just as in AD, there is an increase in tau protein levels without a change in tau mRNA expression, suggesting that Abeta peptides may influence tau protein stability in both the rat and the human brain.
Chambers
C B
CB
Department of Pharmacology and Experimental Therapeutics, Loyola University Medical Center, Maywood, Illinois, 60153, USA.
Sigurdsson
E M
EM
Hejna
M J
MJ
Lorens
S A
SA
Lee
J M
JM
Muma
N A
NA
D017398:Alternative Splicing / Q000187:drug effects; D000544:Alzheimer Disease / Q000378:metabolism; D000679:Amygdala / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D007536:Isomerism; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016875:tau Proteins / Q000032:analysis / Q000737:chemistry / Q000235:genetics*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D012333:RNA, Messenger; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D016875:tau Proteins