Impaired cognition and cerebral glucose regulation are associated with astrocyte activation in the parenchyma of metabolically stressed APPswe/PS1dE9 mice.
Although metabolic syndrome was suggested to be a risk factor for Alzheimer's disease (AD), the role of metabolic stress in the initiation of AD pathology remains unclear. In this study, metabolic stress was induced by a high-fat diet and low-dose injection of streptozotocin (HFSTZ) before the appearance of senile plaques in APP/PS1 transgenic mice. We found that, HFSTZ treatment exacerbated amyloid beta burden and astrocyte activation in the vicinity of plaques. Moreover, we observed an upregulation of astrocytic S100B expression in the brain parenchyma of HFSTZ-treated APP/PS1 mice concurrent with increased interleukin-6 expression in cerebral microvascular cells. To determine the impact of HFSTZ treatment on brain function, we performed [(18)F]fludeoxyglucose-positron emission tomography and analyzed nesting behavior. HFSTZ treatment impaired nest construction and cerebral glucose metabolism in several brain regions of APP/PS1 mice during the early stage of AD. These results suggest that HFSTZ-induced peripheral metabolic stress may contribute to vascular inflammation and astrocyte reactivity in the parenchyma and may impair activity of daily living skill and cerebral glucose metabolism in APP/PS1 mice.
Institute of Neuroscience, Brain Research Center, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Chi-Wen
CW
Yeh
Brain Research Center, National Yang Ming University, Taipei, Taiwan, Republic of China; Biophotonic and Molecular Imaging Research Center, National Yang Ming University, Taipei, Taiwan, Republic of China.
Skye Hsin-Hsien
SH
Yeh
Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County, Taiwan, Republic of China.
Feng-Shiun
FS
Shie
Department of Psychology, Graduate Institute of Brain and Mind Sciences, Neurobiology and Cognitive Science Center, National Taiwan University, Taipei, Taiwan, Republic of China.
Wen-Sung
WS
Lai
Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China; Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, Taiwan, Republic of China.
Hui-Kang
HK
Liu
Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Tsai-Teng
TT
Tzeng
Institute of Neuroscience, Brain Research Center, School of Life Science, National Yang-Ming University, Taipei, Taiwan, Republic of China. Electronic address: hjtsay@ym.edu.tw.
Huey-Jen
HJ
Tsay
Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan, Republic of China; Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, Taiwan, Republic of China; Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei, Taiwan, Republic of China. Electronic address: yshiao@nricm.edu.tw.
Young-Ji
YJ
Shiao
D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D003072:Cognition Disorders / Q000209:etiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology; D008822:Mice, Transgenic; D055806:Microvessels / Q000378:metabolism; D009765:Obesity / Q000209:etiology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D013311:Streptozocin; D013312:Stress, Physiological / Q000502:physiology*
D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D064568:S100 Calcium Binding Protein beta Subunit; C579159:S100b protein, mouse; C528900:glial fibrillary astrocytic protein, mouse; D013311:Streptozocin; D005947:Glucose
Alzheimer's disease; Amyloid plaque; Astrocytes; Cerebral glucose regulation; Cognitive dysfunction; Metabolic stresses