Pinocembrin protected cerebral cortex ultrastructure and inhibited receptor for advanced glycation end products (RAGE) expression against amyloid-β peptide (Aβ)25-35-induced toxicity. (A) Ultrastructural analysis of cerebral cortex against Aβ25-35-induced toxicity. (a,b) The representative area of sham mice cortex was characterized by the normal appearance of neurons, surrounding astrocytes and neuropil. Neurons (N) showed neither swelling nor shrinkage. Astrocytes (As) did not exhibit any apparent signs of perivascular edema. The neuropil appeared compact. (c,d) In the cortex of Aβ25-35-treated mice, neurons (N) showed degenerative changes. The cell membrane was ruptured, and the cell cytoplasm showed dark and dense granules. The nucleolus showed degenerative changes and the karyoplasm was filled with dense materials. Astrocyte (As) foot surrounding the neuron appeared swollen, producing an area of lower tissue density. (e,f) The 40 mg/kg pinocembrin treatment markedly attenuated damage of neuropil in the cortex. Neuronal pycnosis was relieved. The swelling of astrocytes (As) and disintegration of astrocytic cytoplasm was less apparent. (g,h) The 20 mg/kg pinocembrin treatment also alleviated neuronal pycnosis, and the neuropil in the treatment group appeared compact. (B) Fluoro-Jade B staining assay for cortical neuronal degeneration in Aβ25-35-infused mice. (a), sham; (b), Aβ25-35; (c), 20 mg/kg pinocembrin treatment; (d), 40 mg/kg pinocembrin treatment (× 100); (e), mean number of Fluoro-Jade B positive cells/mm2 of the cerebral cortex. Data are presented as the mean ± SEM, n = 4, ***P < 0.001 vs sham, #P < 0.05, ###P < 0.001 vs Aβ25-35. (C) Quantitative real-time polymerase chain reaction (PCR) for mouse RAGE mRNA in cerebral cortex in Aβ25-35-infused mice. Data are presented as the mean ± SEM, n = 5, ***P < 0.001 vs sham, ###P < 0.001 vs Aβ25-35. (D) Western blot analysis for mouse RAGE protein in cerebral cortex in Aβ25-35-infused mice. Data are presented as the mean ± SEM, n = 5, ***P < 0.001 vs sham, ###P < 0.001 vs Aβ25-35.
Liu et al. BMC Medicine 2012 10:105 doi:10.1186/1741-7015-10-105