Ming Tong1, Raiane Leão2, Gina V Vimbela3, Emine B Yalcin4, Jared Kay4, Alexander Krotow5, Suzanne M de la Monte6. 1. Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States. 2. Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. 3. Department of Chemical Engineering, California State University, Long Beach, CA, United States. 4. Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States. 5. Pathobiology Graduate Program, Brown University, United States. 6. Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Division of Neuropathology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Department of Pathology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Department of Neurology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States; Department of Neurosurgery, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, United States. Electronic address: Suzanne_DeLaMonte_MD@Brown.edu.
Abstract
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.
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 matterlipid 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.
Authors: Jeffrey M Burns; Jessica A Church; David K Johnson; Chengjie Xiong; Daniel Marcus; Anthony F Fotenos; Abraham Z Snyder; John C Morris; Randy L Buckner Journal: Arch Neurol Date: 2005-12