Blood Flow Deficits and Cerebrovascular Changes in a Dietary Model of Hyperhomocysteinemia

David J. Braun, Erin Abner, Vikas Bakshi, Danielle S. Goulding, Elizabeth M. Grau, Ai Ling Lin, Christopher M. Norris, Tiffany L. Sudduth, Scott J. Webster, Donna M. Wilcock, Linda J. Van Eldik

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Elevated homocysteine in the blood, or hyperhomocysteinemia, is a recognized risk factor for multiple causes of dementia including Alzheimer’s disease. While reduction of homocysteine levels can generally be accomplished in a straightforward manner, the evidence regarding the cognitive benefits of this approach is less clear. To identify adjunct therapeutic targets that might more effectively restore cognition, the present series of experiments characterizes early and later cerebrovascular changes in a model of hyperhomocysteinemia. Sex-balanced groups of adult C57BL/6J mice were administered a diet deficient in vitamins B6, B12, and B9 (folate) and supplemented with excess methionine. They were subsequently assessed for changes in cerebral blood flow, memory, blood–brain barrier permeability, and selected vascular-associated genes. Blood flow deficits and barrier permeability changes occurred alongside changes in memory and in genes associated with metabolism, endothelial nitric oxide signaling, barrier integrity, and extracellular matrix remodeling. Significant sexually dimorphic responses to the diet were also detected. Taken together, these data deepen our understanding of a major contributor to dementia burden.

Original languageEnglish
JournalASN Neuro
Volume11
DOIs
StatePublished - Jul 1 2019

Bibliographical note

Publisher Copyright:
© The Author(s) 2019.

Keywords

  • blood–brain barrier
  • cerebral blood flow
  • cerebrovascular disease
  • dementia
  • vascular biology

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology

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