Exacerbation of ischemia-induced amyloid-beta generation by diabetes is associated with autophagy activation in mice brain.
To evaluate effect of diabetes on transient ischemia-induced brain damage and autophagy activity, streptozotocin (STZ)-induced diabetic mellitus (DM) mice were subjected to transient common carotid artery occlusion (CCAO) operation. After the operation, immunohistochemistry and transmission electron microscopy (EM) were performed to investigate the astrocytes activation, amyloid-beta protein (Abeta) expression and accumulation of autophagy-like vacuoles containing electron-dense material (avd); and hallmarks of autophagy, the microtubule-associated protein light chain 3 (LC3)-II, was detected by western blot analysis. The results showed that DM amplified stroke-induced astrocytes activation and Abeta generation. Western blot analysis showed that LC3-II conjugate was drastically up-regulated at early stages post ischemia and it last for at least 72h in DM mice brain. DM mice demonstrated increased baseline level of LC3-II as comparing to normal mice; DM also amplified stroke-induced LC3-II level. Under EM, avd was most markedly accumulated in neurons of DM mice brain after ischemia. Immunofluorescence double-staining showed that most Abeta and autophagosomes co-localized. Therefore, our results suggested that exacerbation of ischemia-induced Abeta generation by diabetes might be associated with autophagy activation in mice brain, and modulating neuronal autophagy might be a new therapeutic strategy to depress the risk of development of dementia in diabetic patients with stroke.
Zhang
Ting
T
Department of Neurology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Shanghai 200233, China.
Liu
Xueyuan
X
Li
Qiang
Q
Wang
Jue
J
Jia
Weiping
W
Sun
Xiaojiang
X
D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D001343:Autophagy; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis
D016229:Amyloid beta-Peptides; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins