Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma

Lance A. Johnson, Kristen L. Zuloaga, Tara L. Kugelman, Kevin S. Mader, Jeff T. Morré, Damian G. Zuloaga, Sydney Weber, Tessa Marzulla, Amelia Mulford, Dana Button, Jonathan Lindner, Nabil Alkayed, Jan F. Stevens, Jacob Raber

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors.

Original languageEnglish (US)
Pages (from-to)26-42
Number of pages17
JournalEBioMedicine
Volume3
DOIs
StatePublished - Jan 1 2016

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Keywords

  • Brain
  • Cerebrovascular
  • Cognitive
  • Diabetes
  • Metabolic syndrome
  • Obesity
  • Plasma

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Johnson, L. A., Zuloaga, K. L., Kugelman, T. L., Mader, K. S., Morré, J. T., Zuloaga, D. G., Weber, S., Marzulla, T., Mulford, A., Button, D., Lindner, J., Alkayed, N., Stevens, J. F., & Raber, J. (2016). Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma. EBioMedicine, 3, 26-42. https://doi.org/10.1016/j.ebiom.2015.12.008