Reduced cognitive function, increased bloodbrain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr-/-And C57BL/6 mice fed a western diet

Jennifer M. Rutkowsky, Linda L. Lee, Michelle Puchowicz, Mari S. Golub, Douglas E. Befroy, Dennis W. Wilson, Steven Anderson, Gary Cline, Jason Bini, Kamil Borkowski, Trina A. Knotts, John C. Rutledge

Research output: Contribution to journalArticle

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Abstract

Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/-And microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways.

Original languageEnglish (US)
Article numbere0191909
JournalPloS one
Volume13
Issue number2
DOIs
StatePublished - Feb 1 2018

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blood-brain barrier
Nutrition
Metabolites
Inbred C57BL Mouse
cognition
Cognition
Brain
inflammation
metabolites
brain
mice
Metabolism
Blood-Brain Barrier
Lipids
metabolism
lipids
Diet
factor VIII
Magnetic resonance spectroscopy
LDL Receptors

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Reduced cognitive function, increased bloodbrain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr-/-And C57BL/6 mice fed a western diet. / Rutkowsky, Jennifer M.; Lee, Linda L.; Puchowicz, Michelle; Golub, Mari S.; Befroy, Douglas E.; Wilson, Dennis W.; Anderson, Steven; Cline, Gary; Bini, Jason; Borkowski, Kamil; Knotts, Trina A.; Rutledge, John C.

In: PloS one, Vol. 13, No. 2, e0191909, 01.02.2018.

Research output: Contribution to journalArticle

Rutkowsky, JM, Lee, LL, Puchowicz, M, Golub, MS, Befroy, DE, Wilson, DW, Anderson, S, Cline, G, Bini, J, Borkowski, K, Knotts, TA & Rutledge, JC 2018, 'Reduced cognitive function, increased bloodbrain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr-/-And C57BL/6 mice fed a western diet', PloS one, vol. 13, no. 2, e0191909. https://doi.org/10.1371/journal.pone.0191909
Rutkowsky, Jennifer M. ; Lee, Linda L. ; Puchowicz, Michelle ; Golub, Mari S. ; Befroy, Douglas E. ; Wilson, Dennis W. ; Anderson, Steven ; Cline, Gary ; Bini, Jason ; Borkowski, Kamil ; Knotts, Trina A. ; Rutledge, John C. / Reduced cognitive function, increased bloodbrain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr-/-And C57BL/6 mice fed a western diet. In: PloS one. 2018 ; Vol. 13, No. 2.
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