Unilateral amyloid-beta25-35 injection into the rat amygdala increases the expressions of aberrant tau phosphorylation kinases.
BACKGROUND
Neuropathologically, Alzheimer disease (AD) is characterized by the presence of extracellular plaques enriched in beta-amyloid peptides; however, the mechanism by which it results in the neurotoxicity is uncertain. The purpose of this study was to investigate whether it would prompt the progress of Alzheimer disease via enhancement of aberrant phosphorylated tau that results from its increased kinase gene expression.


METHODS
Twenty-four male rats were divided into three groups, and each group had 8 rats: control, sham-operated, and Abeta(25-35) injected AD model groups. AD rat models were created by unilateral injections of Abeta(25-35) into the amygdala. The hyperphosphorylated tau protein was estimated by immunohistochemistry with paired helical filament-1 (PHF-1) antibody and paired helical filament-tau (AT8) antibody. The expressions of glycogen synthase kinase-3beta (GSK-3beta) and p38 mitogen-activated protein kinase (P(38)MAPK) mRNA were observed by in situ hybridization.


RESULTS
Compared with the control and sham-operated groups, the evaluation of paired AT8 and paired helical filament-1 (PHF-1) in the cortexes and hippocampus of the AD model group showed the numbers of AT8 and PHF-1 positive cells, as well as the optical density (OD) values of the proteins were significantly higher (AT8: in CA2: 0.318 +/- 0.037 vs. 0.135 +/- 0.028, 0.136 +/- 0.031; in frontal cortex: 0.278 +/- 0.040 vs. 0.130 +/- 0.028, 0.190 +/- 0.037. PHF-1: in CA2: 0.386 +/- 0.034 vs. 0.139 +/- 0.010, 0.193 +/- 0.041; in frontal cortex: 0.395 +/- 0.050 vs. 0.159 +/- 0.030, 0.190 +/- 0.044, respectively, P < 0.01); the number of GSK-3beta mRNA and P(38)MAPK mRNA positive cells of the AD model group, as well as the OD values, also increased significantly in the cortexes, hippocampus (GSK-3beta-mRNA: in CA2: 0.384 +/- 0.012 vs. 0.190 +/- 0.015, 0.258 +/- 0.064; in frontal cortex: 0.398 +/- 0.018 vs. 0.184 +/- 0.031, 0.218 +/- 0.049. P(38)MAPK mRNA: in CA2: 0.409 +/- 0.038 vs. 0.161 +/- 0.041, 0.189 +/- 0.035; in frontal cortex: 0.423 +/- 0.070 vs. 0.160 +/- 0.032, 0.203 +/- 0.053, respectively, P < 0.01).


CONCLUSIONS
Unilateral injection of Abeta(25-35) into the rat amygdala increases the generation of aberrant phosphorylated tau by increasing GSK-3beta and P(38)MAPK gene expression, that accelerates the process of Alzhemer's disease.
Department of Neurology, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
Jing
J
Huang
Yu-juan
YJ
Chen
Wei-hong
WH
Bian
Jing
J
Yu
Yu-wu
YW
Zhao
Xue-yuan
XY
Liu
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; C085349:PHF-1 monoclonal antibody; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D048051:p38 Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3