Unilateral amyloid-beta25-35 injection into the rat amygdala increases the expressions of aberrant tau phosphorylation kinases / 中华医学杂志(英文版)

ABSTRACT

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>