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Altered temporal lobe white matter lipid ion profiles in an experimental model of sporadic Alzheimer's disease
被引:10
作者:
Tong, Ming
[1
,2
,4
]
Leao, Raiane
[10
]
Vimbela, Gina V.
[9
]
Yalcin, Emine B.
[1
]
Kay, Jared
[1
]
Krotow, Alexander
[8
]
de la Monte, Suzanne M.
[1
,2
,3
,4
,5
,6
,7
]
机构:
[1] Brown Univ, Rhode Isl Hosp, Liver Res Ctr, Warren Alpert Med Sch, Providence, RI 02912 USA
[2] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Gastroenterol, Providence, RI 02912 USA
[3] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Neuropathol, Providence, RI 02912 USA
[4] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Med, Providence, RI 02912 USA
[5] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Pathol, Providence, RI 02912 USA
[6] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Neurol, Providence, RI 02912 USA
[7] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Neurosurg, Providence, RI 02912 USA
[8] Brown Univ, Pathobiol Grad Program, Providence, RI 02912 USA
[9] Calif State Univ Long Beach, Dept Chem Engn, Long Beach, CA 90840 USA
[10] Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil
基金:
美国国家卫生研究院;
关键词:
Alzheimer;
White matter degeneration;
Streptozotocin;
MALDI;
Imaging mass spectrometry;
BRAIN INSULIN-RESISTANCE;
GROWTH-FACTOR EXPRESSION;
CENTRAL-NERVOUS-SYSTEM;
MASS-SPECTROMETRY;
NATIONAL INSTITUTE;
COGNITIVE DECLINE;
NEUROPATHOLOGIC ASSESSMENT;
ASSOCIATION GUIDELINES;
CEREBRAL ATROPHY;
SULFATIDE;
D O I:
10.1016/j.mcn.2017.04.010
中图分类号:
Q189 [神经科学];
学科分类号:
071006 ;
摘要:
Background: White matter is an early and important yet under-evaluated target of Alzheimer's disease (AD). Metabolic impairments due to insulin and insulin-like growth factor resistance contribute to white matter degeneration because corresponding signal transduction pathways maintain oligodendrocyte function and survival. Methods: This study utilized a model of sporadic AD in which adult Long Evans rats administered intracerebral streptozotocin (i.c. STZ) developed AD-type neurodegeneration. Temporal lobe white matter lipid ion profiles were characterized by matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS). Results: Although the lipid ion species expressed in the i.c. STZ and control groups were virtually identical, i.c. STZ mainly altered the abundances of various lipid ions. Correspondingly, the i.c. STZ group was distinguished from control by principal component analysis and data bar plots. i.c. STZ mainly reduced expression of lipid ions with low m/z's (less than 810) as well as the upper range m/z lipids (m/z 964-986), and increased expression of lipid ions with m/z's between 888 and 937. Phospholipids were mainly included among the clusters inhibited by i.c. STZ, while both sulfatides and phospholipids were increased by i.c. STZ. However, Chi-Square analysis demonstrated significant i.c. STZ-induced trend reductions in phospholipids and increases in sulfatides (P < 0.00001). Conclusions: The i.c. STZ model of sporadic AD is associated with broad and sustained abnormalities in temporal lobe white matter lipids. The findings suggest that the i.c. STZ model could be used for pre-clinical studies to assess therapeutic measures for their ability to restore white matter integrity in AD. (C) 2017 Elsevier Inc. All rights reserved.
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页码:23 / 34
页数:12
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