A High-Cholesterol Diet Increases 27-Hydroxycholesterol and Modifies Estrogen Receptor Expression and Neurodegeneration in Rabbit Hippocampus

Details

• Personal Author:
  Brooks SW ; Dykes AC ; Schreurs BG
• Description:
  Hypercholesterolemia has been implicated in numerous health problems from cardiovascular disease to neurodegeneration. High serum cholesterol levels in midlife have been associated with an increased risk of developing Alzheimer's disease (AD) later in life which suggests that the pathways leading to AD pathology might be activated decades before the symptoms of the disease are detected. Cholesterol-fed animals, particularly cholesterol-fed rabbits, exhibit brain pathology similar to the changes found in brains of AD patients. Dietary cholesterol, which cannot pass the blood-brain barrier, is thought to influence central nervous system homeostasis by increased transport of its circulatory breakdown product, 27-hydroxycholesterol (27-OHC), into the brain. 27-OHC is an endogenous selective estrogen receptor modulator. Estrogenmediated non-reproductive functions require estrogen receptors (ERs) and include modulation of mitochondrial function and structure, as well as regulation of synaptogenesis in the brain. ERs are located in brain areas affected early in AD pathogenesis, including the hippocampus. Here we report that increase in serum cholesterol, induced by feeding rabbits a high-cholesterol diet, is associated with higher levels of 27-OHC in the brain as well as increased levels of neurodegeneration in the hippocampus. Furthermore, these results are accompanied by changes in expression of ERs in the hippocampus as well as a decrease in hippocampal mitochondria. These findings provide an important insight into one of the possible mechanisms involved in the development of AD, and shed light on the processes that may antedate amyloid- and tau phosphorylation changes currently hypothesized to cause AD symptomology and pathology. [Description provided by NIOSH]
• Subjects:
  Aging Animals Blood Cardiovascular Diseases Cardiovascular System Diet Estrogens Occupational Health Pathology Safety
• Keywords:
  27-hydroxycholesterol Age Groups Author Keywords: Alzheimer's Disease Cardiovascular System Disease Cardiovascular System Disorders Central Nervous System Cholesterol Cholesterol-fed Rabbit Dietary Effects ERa ERB Estrogen Receptors Health Effects Mitochondria Oxysterol PSD-95 Synapse

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• ISSN:
  1387-2877
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  85-196
• Volume:
  56
• Issue:
  1
• NIOSHTIC Number:
  nn:20050768
• Citation:
  J Alzheimers Dis 2017 Jan; 56(1):185-196
• Contact Point Address:
  Sylwia W. Brooks, West Virginia University, Blanchette Rockefeller Neurosciences Institute, 8 Medical Center Drive, Morgantown, WV 26506
• Email:
  smrowka@mix.wvu.edu
• Federal Fiscal Year:
  2017
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Alzheimer's Disease
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:487d31c204f045511dc3662831c69a78497736b99f88ac25ecf3edb5f955720ec0b5b269a3f43718999f0791a5a5e74ecd1990fb43bfa559e1ac6a2346d1dbb6
• Download URL:
  https://stacks.cdc.gov/view/cdc/210989/cdc_210989_DS1.pdf
• File Type:
  [PDF - 9.75 MB ]