title: Autophagy-lysosome dysfunction is involved in Aβ deposition in STZ-induced diabetic rats.
abstract: β-Amyloid (Aβ) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce Aβ deposition in the brain, but the mechanism is not fully elucidated. Autophagy-lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)-induced diabetic rats to investigate whether autophagy-lysosome is related to Aβ1-42clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p<0.05) in the Morris water maze test. Meanwhile, hippocampal neuron damage and apoptosis (p<0.05) were found in the DM rats. The Aβ1-42expression in the hippocampus significantly increased in the DM group compared with the control group (p<0.05). The markers of autophagy, beclin-1 and LC3 II, were increased (p<0.05), whereas LC3 I was decreased (p<0.05), and the ratio of LC3 II / I was increased as the time advanced (p<0.01). LAMP1 and LAMP2, which are the markers of lysosome function, were decreased in the hippocampus of DM rats (p<0.05). The Aβ1-42deposition was correlated with beclin-1, LC3 II, and LC3 I positively (p<0.05), but with LAMP1 and LAMP2 negatively (p<0.05). These findings indicate that DM activated autophagy, but lysosome function was impaired. Autophagy-lysosome dysfunction may be involved in the Aβ deposition in diabetic cognitive impairment.
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; The Second Department of Geriatrics, Xi'an Ninth Hospital, Xi'an, China.
authors: Lou-Yan
authors: LY
authors: Ma
authors: The Second Department of Geriatrics, Xi'an Ninth Hospital, Xi'an, China.
authors: Ya-Li
authors: YL
authors: Lv
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Kang
authors: K
authors: Huo
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Jie
authors: J
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Su-Hang
authors: SH
authors: Shang
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Yu-Lang
authors: YL
authors: Fei
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Yan-Bo
authors: YB
authors: Li
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Bei-Yu
authors: BY
authors: Zhao
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Meng
authors: M
authors: Wei
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors: Yong-Ning
authors: YN
authors: Deng
authors: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: quqiumin@medmail.com.cn.
authors: Qiu-Min
authors: QM
authors: Qu
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects*; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D020287:In Situ Nick-End Labeling; D008247:Lysosomes / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin / Q000633:toxicity*
chemical_list: D016229:Amyloid beta-Peptides; D000903:Antibiotics, Antineoplastic; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D013311:Streptozocin; C526109:Anxa3 protein, rat; C075222:amyloid beta-protein (1-42)
keywords: Alzheimer disease; Autophagy; Diabetes mellitus; Lysosome function; β-Amyloid deposition