title: Changes in astrocyte functional markers and β-amyloid metabolism-related proteins in the early stages of hypercholesterolemia.
abstract: Cholesterol is an essential substance for maintaining normal structure and function of the brain. But unfortunately, a long-term high-cholesterol diet can lead to a variety of pathological changes of the brain such as β-amyloid (Aβ) accumulation, Tau hyperphosphorylation, reactive gliosis, neuroinflammation, neuronal death and synaptic degeneration. These pathological changes have complex internal relations with one other, causing memory impairment and participating in the pathogenesis of Alzheimer's disease (AD). However, early hypercholesterolemia-induced events that lead to brain deterioration are not clear. To address this, 6-month-old female mice were fed a 3% cholesterol diet for 8weeks, followed by behavioral, biochemical and neuropathological analyses. The high-cholesterol-fed mice did not show neuronal and synaptic impairment or cognitive deficits compared with mice given a normal diet, but astrocytes were mildly activated with increased expression of functional markers including apolipoprotein E and aquaporin 4 in the hippocampus. Hippocampal interleukin-1β expression slightly increased, but interleukin-6 (IL-6) and tumor necrosis factor-α did not change significantly compared with those in the control group. Levels of Aβ, and its precursor protein, were unaffected, but levels of presenilin 1 and insulin-degrading enzyme (IDE), that initiate Aβ generation and degradation, respectively, increased in the hippocampus of the model mice. In addition, Tau phosphorylation levels were not different between the control and model groups. These results suggest that changes in astrocyte functional markers and Aβ metabolism proteins, which contribute to maintaining brain cholesterol and Aβ homeostasis, are early events in the process of hypercholesterolemia-related neuropathological changes.
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: L M
authors.initials: LM
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Gao
authors.affiliation: Department of Rehabilitation Sciences, University of Kentucky Center of Excellence in Rural Health, Hazard, KY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Marshall
authors.affiliation: Department of Neurology, Shiyan Renmin Hospital, Hubei University of Medicine, No 39 Chaoyang Middle Road, Shiyan, Hubei Province 442000, People's Republic of China.
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Cai
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China.
authors.forename: G
authors.initials: G
authors.lastname: Hu
authors.affiliation: Jiangsu Key Laboratory of Neurodegeneration, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China. Electronic address: mingx@njmu.edu.cn.
authors.forename: M
authors.initials: M
authors.lastname: Xiao
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism*; D001835:Body Weight; D001921:Brain / Q000473:pathology*; D002452:Cell Count; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D006937:Hypercholesterolemia / Q000097:blood* / Q000473:pathology*; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051401:Aquaporin 4; D016207:Cytokines; D027342:Excitatory Amino Acid Transporter 2; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C493396:Slc1a2 protein, mouse; D002784:Cholesterol; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491234:Adam10 protein, mouse
keywords: Alzheimer’s disease; astrocytes; hypercholesterolemia; neuroinflammation; β-amyloid