Disrupted iron metabolism and ensuing oxidative stress may mediate cognitive dysfunction induced by chronic cerebral hypoperfusion.
Iron is a highly reactive free radical catalyst that has been shown to exacerbate oxidative stress and cell death in many neurodegenerative diseases. In this study, we produced a rat model of chronic cerebral hypoperfusion (CCH) by permanent bilateral carotid artery occlusion to investigate markers of iron and oxidative stress associated with it. We found CCH led to significant spatial memory impairment in the Morris water maze at 4 months after bilateral ligation. Iron deposition was observed in both the hippocampal CA1 area and cerebral cortex, and was correlated with localized neuronal death and increased lipid peroxidation. Western blotting revealed that the expression levels of ferritin heavy chain and the transferrin receptor were significantly elevated in hippocampus and cortex after CCH, whereas expression of iron regulatory protein 1 was significantly lower than in sham-treated rats. We conclude that localized neurodegeneration and concomitant cognitive impairments following CCH may result, at least in part, from local disruption of neuronal iron metabolism.
Department of Neurology, Tongji Hospital, Tongji University, 389 Xincun Road, Shanghai, China.
Yunxia
Y
Li
Yusheng
Y
He
Qiang
Q
Guan
Wuchao
W
Liu
Hongjie
H
Han
Zhiyu
Z
Nie
D000818:Animals; D001052:Apoferritins / Q000819:agonists / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology*; D056547:CA1 Region, Hippocampal / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation; D007501:Iron / Q000378:metabolism*; D035941:Iron Regulatory Protein 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000819:agonists / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation
D009419:Nerve Tissue Proteins; D011990:Receptors, Transferrin; C545564:Tfrc protein, rat; D001052:Apoferritins; D007501:Iron; D035941:Iron Regulatory Protein 1